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【结 构 式】

【分子编号】23933

【品名】2-Propanamine; Isopropylamine

【CA登记号】75-31-0

【 分 子 式 】C3H9N

【 分 子 量 】59.1112

【元素组成】C 60.96% H 15.35% N 23.7%
与该中间体有关的原料药合成路线共 35 条
合成路线1合成路线2合成路线3合成路线4合成路线5合成路线6合成路线7合成路线8合成路线9合成路线10合成路线11合成路线12合成路线13合成路线14合成路线15合成路线16合成路线17合成路线18合成路线19合成路线20合成路线21合成路线22合成路线23合成路线24合成路线25合成路线26合成路线27合成路线28合成路线29合成路线30合成路线31合成路线32合成路线33合成路线34合成路线35

合成路线1

该中间体在本合成路线中的序号：(IV)

By condensation of 4-hydroxycarbazole (I) with epichlorohydrin (II) by means of NaOH in aqueous dioxane at 40 C to yield 4-(2,3-epoxypropoxy)carbazole (III), followed by treatment with isopropylamine (IV) in refluxing ethanol

参考文献 中间体
合成目标
【1】 Weetman, D.F.; Castaner, J.; Carazolol. Drugs Fut 1977, 2, 11, 715.
【2】 Leinert, H.; et al. (Boehringer Ingelheim GmbH); Triyclic diphenylamines derivatives. CH 598216; DE 2240599; FR 2196165; GB 1369580; JP 49056973 .
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(I) 29480 4-Hydroxycarbazole; 9H-carbazol-4-ol 52602-39-8 C12H9NO 详情 详情
(II) 10146 Epichlorohydrin; 2-(Chloromethyl)oxirane 106-89-8 C3H5ClO 详情 详情
(III) 40171 9H-carbazol-4-yl 2-oxiranylmethyl ether; 4-(2-oxiranylmethoxy)-9H-carbazole 51997-51-4 C15H13NO2 详情 详情
(IV) 23933 2-Propanamine; Isopropylamine 75-31-0 C3H9N 详情 详情

合成路线2

该中间体在本合成路线中的序号：(V)

The esterification of 3-(4-hydroxyphenyl)propionic acid (I) with methanol and H2SO4 gives the corresponding methyl ester (II), which by condensation with epichlorohydrin (III) by means of K2CO3 in refluxing acetone affords methyl 3-[4-(2,3-epoxypropoxy)phenyl]propionate (IV). Finally, the epoxide ring is opened by reaction with isopropylamine (V) in refluxing methanol, and a final treatment with ethereal HCl is performed.

参考文献 中间体
合成目标
【1】 Erhardt, P.W.; Woo, C.M.; Anderson, W.G.; Gorczynski, R.J.; Ultra-short-acting beta-adrenergic receptor blocking agents. 2. (Aryloxy)propanolamines containing esters on the aryl function. J Med Chem 1982, 25, 12, 1408.
【2】 Erhardt, P.W.; Bogman, R.J.; O'Donnell, J.P. (Baxter International Inc.); Method for treatment or prophylaxis of cardiac disorders. EP 0053435; EP 0065542; US 4387103; WO 8201869 .
【3】 Serradell, M.N.; Castaner, J.; Badia, A.; Esmolol Hydrochloride. Drugs Fut 1984, 9, 3, 183.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(I) 25691 3-(4-hydroxyphenyl)propionic acid 501-97-3 C9H10O3 详情 详情
(II) 30341 methyl 3-(4-hydroxyphenyl)propanoate; 4-Hydroxyphenylpropionic acid methyl ester; 3-(4-Hydroxyphenyl)propionic acid methyl ester 5597-50-2 C10H12O3 详情 详情
(III) 10146 Epichlorohydrin; 2-(Chloromethyl)oxirane 106-89-8 C3H5ClO 详情 详情
(IV) 30342 methyl 3-[4-(2-oxiranylmethoxy)phenyl]propanoate 81147-94-6 C13H16O4 详情 详情
(V) 23933 2-Propanamine; Isopropylamine 75-31-0 C3H9N 详情 详情

合成路线3

该中间体在本合成路线中的序号：(C)

The condensation of ethyl p-hydroxyphenylacetate (I) with benzyl chloride (II) by means of sodium ethoxide in refluxing ethanol gives ethyl p-(benzyloxy)phenylacetate (III), which is reduced with LiAlH4 in THF to 2-(p-benzyloxyphenyl)ethanol (IV). The etherification of (IV) with cyclopropyl bromide (A) by means of NaH in hot DMF affords 4-(cyclopropylmethoxyethyl)-1-benzyloxybenzene (V), which is debenzylated by hydrogenation with H2 and Pd/C in methanol giving rise to p-(cyclopropylmethoxyethyl)phenol (VI). The condensation of (VI) with epichlorohydrin (B) by means of NaOH in water yields 1-[p-(cyclopropylmethoxyethyl)phenoxy]-2,3-epoxypropane (VII), which is treated with isopropylamine (C) and finally with HCl in ether.

参考文献 中间体
合成目标
【1】 Manoury, P.M.J.; et al. (Sanofi-Synthelabo ); Phenol ethers. DE 2649605; FR 2330383; GB 1515978; JP 52085146; US 4252984 .
【2】 Hillier, K.; Castaner, J.; Serradell, M.N.; Blancafort, P.; Betaxolol hydrochloride. Drugs Fut 1979, 4, 12, 867.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(B) 10146 Epichlorohydrin; 2-(Chloromethyl)oxirane 106-89-8 C3H5ClO 详情 详情
(A) 22277 Cyclopropyl bromide; 1-(Bromomethyl)cyclopropane 7051-34-5 C4H7Br 详情 详情
(I) 24994 Ethyl 2-(4-hydroxyphenyl)acetate 17138-28-2 C10H12O3 详情 详情
(II) 19171 1-(Chloromethyl)benzene; Benzyl chloride 100-44-7 C7H7Cl 详情 详情
(III) 28637 Ethyl 2-[4-(benzyloxy)phenyl]acetate; p-(Benzyloxy)phenylacetate C17H18O3 详情 详情
(IV) 33328 2-(p-Benzyloxyphenyl)ethanol; 2-[4-(Benzyloxy)phenyl]-1-ethanol C15H16O2 详情 详情
(V) 33329 4-(Cyclopropylmethoxyethyl)-1-benzyloxybenzene; 1-(Benzyloxy)-4-[2-(cyclopropylmethoxy)ethyl]benzene; Benzyl 4-[2-(cyclopropylmethoxy)ethyl]phenyl ether C19H22O2 详情 详情
(VI) 33330 4-[2-(Cyclopropylmethoxy)ethyl]phenol; p-(Cyclopropylmethoxyethyl)phenol C12H16O2 详情 详情
(VII) 33331 2-([4-[2-(Cyclopropylmethoxy)ethyl]phenoxy]methyl)oxirane; 1-[p-(Cyclopropylmethoxyethyl)phenoxy]-2,3-epoxypropane; 4-[2-(Cyclopropylmethoxy)ethyl]phenyl 2-oxiranylmethyl ether C15H20O3 详情 详情
(C) 23933 2-Propanamine; Isopropylamine 75-31-0 C3H9N 详情 详情

合成路线4

该中间体在本合成路线中的序号：(VII)

The reaction of 3,4-dihydro-2H-1-benzopyran-3,8-diol (I) with ethyl chloroformate by means of triethylamine in THF gives 3,4-dihydro-8-lethoxy carbonyloxyl-2H-1-benzopyran-3-ol (II), which is treated with nitric acid and acetic anhydride in acetonitrile to yield 3,4-dihydro-8-(ethoxycarbonyloxy)-2H-1-benzopyran-3-ol-3-nitrate (III). The hydrolysis of (III) with NaOH in methanol affords 3,4-dihydro-8-hydroxy-2H-1-benzopyran-3-ol 3-nitrate (IV), which is condensed with epichlorohydrin (V) by means of NaOH in water giving 3,4-dihydro-8-(2,3-epoxypropoxy)-2H-1-benzopyran-3-ol 3-nitrate (VI). Finally, this compound is treated with isopropylamine in refluxing ethanol.

参考文献 中间体
合成目标
【1】 Shiratsuohi, M.; Shimizu, N.; Shigyo, H.; Kyotani, Y.; Kunieda, H.; Kawamura, K.; Sato, S.; Akashi, T.; Nagakura, M. (Kowa Co., Ltd.); Dihydrobenzopyran compounds and pharmaceutical composition comprising said compounds. EP 0042299; JP 57007481; JP 82106619 .
【2】 Blancafort, P.; Thorpe, P.J.; Serradell, M.N.; Castaner, J.; K-351. Drugs Fut 1983, 8, 6, 497.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(I) 30654 3,8-chromanediol C9H10O3 详情 详情
(II) 30655 ethyl 3-hydroxy-3,4-dihydro-2H-chromen-8-yl carbonate C12H14O5 详情 详情
(III) 30656 ethyl 3-(nitrooxy)-3,4-dihydro-2H-chromen-8-yl carbonate C12H13NO7 详情 详情
(IV) 30657 3-(nitrooxy)-8-chromanol C9H9NO5 详情 详情
(V) 10146 Epichlorohydrin; 2-(Chloromethyl)oxirane 106-89-8 C3H5ClO 详情 详情
(VI) 30658 3-(nitrooxy)-3,4-dihydro-2H-chromen-8-yl 2-oxiranylmethyl ether; 3-(nitrooxy)-8-(2-oxiranylmethoxy)chromane C12H13NO6 详情 详情
(VII) 23933 2-Propanamine; Isopropylamine 75-31-0 C3H9N 详情 详情

合成路线5

该中间体在本合成路线中的序号：(A)

3) A third sequence proceeds by condensation of p-iodobenzaldehyde (IX) with nitromethane, followed by reductive hydrolysis of the intermediate unsaturated nitrocompound, to yield p-iodophenylacetone (VIII). The final sequence is the same as in scheme 09034702a.

参考文献 中间体
合成目标
【1】 le Poncin-Lafitte, M.; Duterte, D.; Morier, E.; et al.; Synthesis of p-I-125 amphetamine. J Label Compd Radiopharm 1983, 20, 149.
【2】 Coornaert, S.; Rapin, J.R.; Bardy, A.; et al.; New ways of obtaining N-isopropyl-p-iodoamphetamine and pharmacokinetic studies in rat. 3rd Wordl Cong Nucl Med Biol (Aug, Paris) 1982, 4, 23, 3598.
【3】 Rapin, J.R.; et al.; Chemical and pharmacological aspects of cerebral cellular tracers. Ann Radiol 1983, 26, 1, 48.
【4】 Baldwin, R.M.; Iofetamine (123I) hydrochloride. Drugs Fut 1986, 11, 8, 652.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(A) 23933 2-Propanamine; Isopropylamine 75-31-0 C3H9N 详情 详情
(V) 24297 1-(4-iodophenyl)-N-isopropyl-2-propanamine C12H18IN 详情 详情
(VIII) 24299 1-(4-iodophenyl)acetone C9H9IO 详情 详情
(IX) 24301 4-iodobenzaldehyde 15164-44-0 C7H5IO 详情 详情

合成路线6

该中间体在本合成路线中的序号：(IV)

1) The reaction of phenol (I) with epichlorohydrin (II) gives 1,2-epoxy-3-phenoxypropane (III), which is treated with isopropylamine (IV) to afford 3-(isopropylamino)-1-phenoxy-2-propanol (V). Cyclization of (V) with diethyl carbonate (VI) yields 3-isopropyl-5-(phenoxymethyloxazolidin-2-one) (VII), which is chloromethylated with formaldehyde - HCl giving 3-isopropyl-5-(4-chloromethylphenoxymethyl)oxazolidin-2-one (VIII). Etherification of (VIII) with ethylene glycol monoisopropyl ether (IX) yields the corresponding ether (XI), which is finally deprotected by alkaline hydrolysis.

参考文献 中间体
合成目标
【1】 Harting, J.; et al.; Pharmacodynamic profile of the selective beta1-adrenoceptor antagonist bisoprolol. Arzneim-Forsch Drug Res 1986, 36, 2, 200.
【2】 Castaner, J.; Prous, J.; Bisoprolol fumarate. Drugs Fut 1986, 11, 10, 829.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(I) 23540 Phenol 108-95-2 C6H6O 详情 详情
(II) 10146 Epichlorohydrin; 2-(Chloromethyl)oxirane 106-89-8 C3H5ClO 详情 详情
(III) 23932 2-(phenoxymethyl)oxirane; oxiranylmethyl phenyl ether 122-60-1 C9H10O2 详情 详情
(IV) 23933 2-Propanamine; Isopropylamine 75-31-0 C3H9N 详情 详情
(V) 23934 1-(isopropylamino)-3-phenoxy-2-propanol C12H19NO2 详情 详情
(VI) 17470 diethyl carbonate; diethylcarbonate 105-58-8 C5H10O3 详情 详情
(VII) 23936 3-isopropyl-5-(phenoxymethyl)-1,3-oxazolidin-2-one C13H17NO3 详情 详情
(VIII) 23937 5-[[4-(chloromethyl)phenoxy]methyl]-3-isopropyl-1,3-oxazolidin-2-one C14H18ClNO3 详情 详情
(IX) 23938 2-isopropoxy-1-ethanol 109-59-1 C5H12O2 详情 详情
(X) 23939 5-([4-[(2-isopropoxyethoxy)methyl]phenoxy]methyl)-3-isopropyl-1,3-oxazolidin-2-one C19H29NO5 详情 详情

合成路线7

该中间体在本合成路线中的序号：(VI)

The condensation of 4-hydroxybenzyl alcohol (I) with 2-isopropoxyethanol (II) by heating at 150 C gives the corresponding benzyl ether (III), which is condensed with epichlorohydrin (IV) to yield the adduct (V). Finally, this compound is treated with isopropylamine in ethanol.

参考文献 中间体
合成目标
【1】 Schliep, H.-J.; Enenkel, H.-J.; Minck, K.; Becker, K.-H.; Jonas, R. (Merck Patent GmbH); Phenoxy-amino-propanols. US 4258062 .
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(I) 29474 4-(hydroxymethyl)phenol; 4-hydroxyphenylmethanol 4-hydroxybenzenemethanol; 4-Hydroxybenzyl alcohol 623-05-2 C7H8O2 详情 详情
(II) 23938 2-isopropoxy-1-ethanol 109-59-1 C5H12O2 详情 详情
(III) 40522 4-[(2-isopropoxyethoxy)methyl]phenol C12H18O3 详情 详情
(IV) 10146 Epichlorohydrin; 2-(Chloromethyl)oxirane 106-89-8 C3H5ClO 详情 详情
(V) 40523 4-[(2-isopropoxyethoxy)methyl]phenyl 2-oxiranylmethyl ether; 2-([4-[(2-isopropoxyethoxy)methyl]phenoxy]methyl)oxirane C15H22O4 详情 详情
(VI) 23933 2-Propanamine; Isopropylamine 75-31-0 C3H9N 详情 详情

合成路线8

该中间体在本合成路线中的序号：(VIII)

The condensation of fluorene-9-carboxamide (IV) with acrylonitrile (V) by means of benzyltrimethylammonium hydroxide (VI) in hot dioxane gives 9-carbamoyl-9-(2-cyanoethyl)fluorene (VII), which is then hydrogenated and condensed with isopropylamine (VIII) and H2 over PtO2 with the same isopropylamine (VIII) as solvent.

参考文献 中间体
合成目标
【1】 Lavagnino, E.R.; Pike, A.J.; Campbell, J.B. (Eli Lilly and Company); 9-Carbamoyl-9-(2-cyanoethyl)fluorenes. DD 158395; EP 0038676; GB 2074161; JP 1125363; US 4282170 .
【2】 Serradell, M.N.; Sneddon, J.; Castaner, J.; Indecainide. Drugs Fut 1985, 10, 2, 121.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(IV) 28969 9H-fluorene-9-carboxamide C14H11NO 详情 详情
(V) 28970 3-butenenitrile 109-75-1 C4H5N 详情 详情
(VI) 27394 Trimethylbenzylammonium Hydroxide; N,N,N-trimethyl(phenyl)methanaminium hydroxide; Triton B; Benzyltrimethylammonium hydroxide 100-85-6 C10H17NO 详情 详情
(VII) 28971 9-(2-cyanoethyl)-9H-fluorene-9-carboxamide C17H14N2O 详情 详情
(VIII) 23933 2-Propanamine; Isopropylamine 75-31-0 C3H9N 详情 详情

合成路线9

该中间体在本合成路线中的序号：(C)

This 1-vinylimidazole compound (II) is obtained by reaction of N,N'-thionyldiimidazole (A) with 2-hydroxy-3,6-dichloroacetophenone (I) in dichloro-methane. Treatment of (II) with epibromohydrin (B) in DMF in the presence of NaH gives the epoxy compound (III), which is then treated with isopropylamine (C) to obtain the propanolamine compound (IV). The hydrochloride can be prepared by treatment of the free base (IV) with one molar equivalent of HCl in AcOEt.

参考文献 中间体
合成目标
【1】 Kida, S.; Ueda, M.; Kimoto, S.; Haruna, M.; Matsumoto, H.; Takahashi, K.; Ogata, M.; Synthesis and antiarrhythmic activity of new 1-[1-[2-[3-(alkylamino)-2-hydroxypropoxy]phenyl]vinyl]-1H-imidazoles and related compounds. J Med Chem 1984, 27, 9, 1142.
【2】 Ueda, M.; 711389-S. Drugs Fut 1985, 10, 6, 472.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(A) 29655 1-(1H-imidazol-1-ylsulfinyl)-1H-imidazole C6H6N4OS 详情 详情
(B) 29679 2-(bromomethyl)oxirane 3132-64-7 C3H5BrO 详情 详情
(I) 29677 1-(3,6-dichloro-2-hydroxyphenyl)-1-ethanone C8H6Cl2O2 详情 详情
(II) 29678 3,6-dichloro-2-[1-(1H-imidazol-1-yl)vinyl]phenol C11H8Cl2N2O 详情 详情
(III) 29680 3,6-dichloro-2-[1-(1H-imidazol-1-yl)vinyl]phenyl 2-oxiranylmethyl ether; 1-[1-[3,6-dichloro-2-(2-oxiranylmethoxy)phenyl]vinyl]-1H-imidazole C14H12Cl2N2O2 详情 详情
(IV) 29681 1-[3,6-dichloro-2-[1-(1H-imidazol-1-yl)vinyl]phenoxy]-3-(isopropylamino)-2-propanol C17H21Cl2N3O2 详情 详情
(C) 23933 2-Propanamine; Isopropylamine 75-31-0 C3H9N 详情 详情

合成路线10

该中间体在本合成路线中的序号：(IV)

The condensation of sodium 2-(2-exo-norbornyl)phenoxide [from 2-bicyclo[2.2.1]hept-2-ylphenol (I) and sodium] with epichlorohydrin (II) gives (III), which is then treated with isopropylamine (IV) and finally with isopropanolic HCl.

参考文献 中间体
合成目标
【1】 FR 75/09997; FR 76/24360 .
【2】 Michaud, R.; Bornaprolol hydrochloride. Drugs Fut 1982, 7, 2, 91.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(I) 37059 2-bicyclo[2.2.1]hept-2-ylphenol C13H16O 详情 详情
(II) 10146 Epichlorohydrin; 2-(Chloromethyl)oxirane 106-89-8 C3H5ClO 详情 详情
(III) 37060 2-[(2-bicyclo[2.2.1]hept-2-ylphenoxy)methyl]oxirane; 2-bicyclo[2.2.1]hept-2-ylphenyl 2-oxiranylmethyl ether C16H20O2 详情 详情
(IV) 23933 2-Propanamine; Isopropylamine 75-31-0 C3H9N 详情 详情

合成路线11

该中间体在本合成路线中的序号：(A)

The condensation of 7-methylindan-4-ol (I) with crotyl chloride (II) by means of NaH in DMF gives 1-(7-methylindan-4-yloxy)-trans-2-butuene (III), which is epoxidized with H2O2 in MeCN-MeOH yielding 1-(7-methylindan-4-yloxy)-trans-2,3-epoxybutane (IV). Finally, this compound is treated with isopropylamine (A) in refluxing water.

参考文献 中间体
合成目标
【1】 Tucker, H. (AstraZeneca plc); Alkanolamine derivs., process for their preparation and pharmaceutical compsns. containing them. EP 0003664 .
【2】 Castaner, J.; Blancafort, P.; Weetman, D.F.; Serradell, M.N.; ICI-118,551. Drugs Fut 1983, 8, 10, 853.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(A) 23933 2-Propanamine; Isopropylamine 75-31-0 C3H9N 详情 详情
(I) 36217 7-methyl-4-indanol 16400-13-8 C10H12O 详情 详情
(II) 36218 (E)-1-chloro-2-butene C4H7Cl 详情 详情
(III) 36219 (E)-2-butenyl 7-methyl-2,3-dihydro-1H-inden-4-yl ether; 4-[(E)-2-butenyloxy]-7-methylindane C14H18O 详情 详情
(IV) 36220 7-methyl-2,3-dihydro-1H-inden-4-yl (3-methyl-2-oxiranyl)methyl ether; 2-methyl-3-[[(7-methyl-2,3-dihydro-1H-inden-4-yl)oxy]methyl]oxirane C14H18O2 详情 详情

合成路线12

该中间体在本合成路线中的序号：(II)

This compound can be prepared by two related ways: 1) The condensation of methoxyacetaldehyde (I) with isopropylamine (II) gives methoxyacetaldehyde isopropylimine (III), which is treated with 4-benzyloxyindole (IV) in acetic acid yielding 4-benzyloxy-3-(1-isopropylamino-2-ethoxyethyl)indole (V). The reaction of (V) with ethyl nitroacetate (VI) in hot toluene affords ethyl 3-(4-benzyloxyindol-3-yl)-2-nitro-5-oxahexanoate (VII), which is reduced with H2 over Raney-Ni in ethanol giving ethyl 3-(4-benzyloxyindol-3-yl)-2-amino-5-oxahexanoate (VIII). Finally, this compound is cyclized with paraformaldehyde (IX) in refluxing benzene. 2) Compound (VIII) can also be cyclized with glyoxylic acid (X) yielding a mixture of the tetrahydrocarboline (XI) and the dihydrocarboline (XII), which, without separation, are decarboxylated and dehydrogenated with sulfur at 140 C.

参考文献 中间体
合成目标
【1】 Neef, G.; Schmiechen, R.; Huth, A.; Eder, U.; Rathz, D.; Seidelmann, D.; Synthesis of 4-sibstituted beta-carbolines. Heterocycles 1983, 20, 7, 1295-1313.
【2】 Neef, G.; Eder, U.; Schmiechen, R.; Huth, A.; Rathz, D.; Seidelmonn, D.; Kehr, W.; Palenschat, D.; Braestrup, C.T.; et al. (Schering AG); Pharmacologically active 3-substituted beta-carbolines. DD 161210; EP 0054507; ES 8301984; US 4435403; US 4596808 .
【3】 Castaner, J.; Serradell, M.N.; ZK-91296. Drugs Fut 1984, 9, 10, 761.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(I) 34354 2-methoxyacetaldehyde 10312-83-1 C3H6O2 详情 详情
(II) 23933 2-Propanamine; Isopropylamine 75-31-0 C3H9N 详情 详情
(III) 34355 N-[(E)-2-methoxyethylidene]-2-propanamine; N-isopropyl-N-[(E)-2-methoxyethylidene]amine C6H13NO 详情 详情
(IV) 31535 4-Benzyloxyindole; 4-(benzyloxy)-1H-indole; benzyl 1H-indol-4-yl ether 20289-26-3 C15H13NO 详情 详情
(V) 34356 N-[1-[4-(benzyloxy)-1H-indol-3-yl]-2-methoxyethyl]-2-propanamine; N-[1-[4-(benzyloxy)-1H-indol-3-yl]-2-methoxyethyl]-N-isopropylamine C21H26N2O2 详情 详情
(VI) 15050 ethyl 2-nitroacetate; Acetic acid, nitro-, ethyl ester 626-35-7 C4H7NO4 详情 详情
(VII) 34357 ethyl 3-[4-(benzyloxy)-1H-indol-3-yl]-4-methoxy-2-nitrobutanoate C22H24N2O6 详情 详情
(VIII) 34358 ethyl 2-amino-3-[4-(benzyloxy)-1H-indol-3-yl]-4-methoxybutanoate C22H26N2O4 详情 详情
(X) 15618 2-Oxoacetic acid; Glyoxylic Acid 298-12-4 C2H2O3 详情 详情
(XI) 34359 5-(benzyloxy)-3-(ethoxycarbonyl)-4-(methoxymethyl)-2,3,4,9-tetrahydro-1H-beta-carboline-1-carboxylic acid C24H26N2O6 详情 详情
(XII) 34360 5-(benzyloxy)-3-(ethoxycarbonyl)-4-(methoxymethyl)-2,4a,9,9a-tetrahydro-1H-beta-carboline-1-carboxylic acid C24H26N2O6 详情 详情

合成路线13

该中间体在本合成路线中的序号：(VI)

The acylation of 8-hydroxy-1,2,3,4-tetrahydroquinoline (I) with nicotinoyl chloride (II) by means of triethylamine in benzene gives 8-hydroxy-1-nicotinoyl-1,2,3,4-tetrahydroquinoline (III), which is condensed with epichlorohydrin (IV) by means of potassium tert-butoxide in DMF to yield 1-nicotinoyl-8-(2,3-epoxy-1-propoxy)-1,2,3,4-tetrahydroquinoline (V). Finally, this compound is condensed with isopropylamine (VI) in ethanol.

参考文献 中间体
合成目标
【1】 Graewinger, O.; Raabe, T.; Beyerle, R.; Scholtholt, J.; Nitz, R.E.; 1-Acyl-8-(3-amino-2-hydroxypropoxy)-1,2,3,4-tetrahydroquinolines, compositions and use. DD 153368; DE 2934609; EP 0025864; JP 56034668; US 4335123 .
【2】 Castaner, J.; Serradell, M.N.; Hillier, K.; Nicainoprol. Drugs Fut 1984, 9, 10, 749.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(I) 16022 1,2,3,4-tetrahydro-8-quinolinol C9H11NO 详情 详情
(II) 10753 Nicotinoyl chloride C6H4ClNO 详情 详情
(III) 34334 [8-hydroxy-3,4-dihydro-1(2H)-quinolinyl](3-pyridinyl)methanone C15H14N2O2 详情 详情
(IV) 10146 Epichlorohydrin; 2-(Chloromethyl)oxirane 106-89-8 C3H5ClO 详情 详情
(V) 34335 [8-(2-oxiranylmethoxy)-3,4-dihydro-1(2H)-quinolinyl](3-pyridinyl)methanone C18H18N2O3 详情 详情
(VI) 23933 2-Propanamine; Isopropylamine 75-31-0 C3H9N 详情 详情

合成路线14

该中间体在本合成路线中的序号：(V)

This compound can be obtained through two different ways from 4-(4-aminophenyl)-1H-imidazole (I): 1) By condensation of compound (I) with ethyl N-isopropylformimidate (II) in ethanol. 2) The reaction of compound (I) with ethyl N-cyanoformimidate (III) gives N'-cyano-N-(4-1H-imidazol-4-ylphenyl)formamidine (IV), which is treated with isopropylamine (V).

参考文献 中间体
合成目标
【1】 Cereda, E.; Donetti, A.; Del Soldato, P.; Bergamoschi, M.; Imidazolylphenyl amidines, pharmaceutical compositions containing same and use thereof. EP 0053407; ES 8207147; ES 8207148; ES 8207149; ES 8207150; ES 8207151; ES 8207152; GB 2088375; JP 57120575; US 4386099; US 4465841 .
【2】 Donetti, A.; et al.; (Imidazoylphenyl)formamidines. A structurally novel class of potent histamine H2-receptor antagonists. J Med Chem 1984, 27, 3, 380-386.
【3】 Serradell, M.N.; de Angelis, L.; Castaner, J.; Mifentidine. Drugs Fut 1984, 9, 11, 825.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(I) 34316 4-(1H-imidazol-4-yl)phenylamine; 4-(1H-imidazol-4-yl)aniline C9H9N3 详情 详情
(II) 34317 ethyl isopropyliminoformate C6H13NO 详情 详情
(III) 24747 ethyl cyanoiminoformate C4H6N2O 详情 详情
(IV) 34318 N-cyano-N'-[4-(1H-imidazol-4-yl)phenyl]iminoformamide C11H9N5 详情 详情
(V) 23933 2-Propanamine; Isopropylamine 75-31-0 C3H9N 详情 详情

合成路线15

该中间体在本合成路线中的序号：(IV)

The Friedel-Crafts condensation of 8-hydroxycarbostyril (I) with 2-bromobutyryl chloride by means of AlCl3 in refluxing CS2 gives 5-(2-bromobutyryl)-8-hydroxycarbostyril (II), which by reaction with isopropylamine in isopropanol affords 5-(2-isopropylaminobutyryl)-8-hydroxycarbostyril (III). Finally, this compound is reduced with NaBH4 in methanol.

参考文献 中间体
合成目标
【1】 Nakagawa, K.; et al.; Dérivés de 5-(1-hydroxy-2-amino substitué)alkyl-8-carbostyryle substitué et de 5-(1-hydroxy-2-amino substitué)alkyl-8-(3,4-dihydro)carbostyryle substitué et leur procédé de préparation. BE 0823841; JP 50095279 .
【2】 Yoshizaki, S.; et al.; Sympathomimetic amines having a carbostyril nucleus. J Med Chem 1976, 19, 9, 35-45.
【3】 Castaner, J.; Weetman, D.F.; Procaterol. Drugs Fut 1978, 3, 2, 135.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(I) 39072 8-hydroxy-2(1H)-quinolinone 15450-76-7 C9H7NO2 详情 详情
(II) 39781 2-bromobutanoyl chloride 22118-12-3 C4H6BrClO 详情 详情
(III) 39782 5-(2-bromobutanoyl)-8-hydroxy-2(1H)-quinolinone C13H12BrNO3 详情 详情
(IV) 23933 2-Propanamine; Isopropylamine 75-31-0 C3H9N 详情 详情
(V) 39783 8-hydroxy-5-[2-(isopropylamino)butanoyl]-2(1H)-quinolinone C16H20N2O3 详情 详情

合成路线16

该中间体在本合成路线中的序号：(B)

Compound can be prepared in several different ways: 1) The reaction of 2-acetyl-7-hydroxybenzofuran (I) with epichlorohydrin by means of piperidine hydrochloride (A) at 105 C gives 2-acetyl-7-(2,3-epoxypropoxy)benzofuran (II), which is then condensed with isopropylamine (B) in refluxing ethanol. 2) By reaction of (I) with 1-chloro-3-isopropylamino-2-propanol (C) by means of NaOH at 80 C in a sealed tube. 3) By reductocondensation of 2-[1,1-(ethylenedioxy)ethyl]-7-[2-oxo-3-(hydroxyimino)propoxy]benzofuran (III) with acetone by means of H2 and PtO2 in ethanol, followed by hydrolysis of the reduced product with HCl in ethanol. 4) The reaction of 2-[1,1-(ethylenedioxy)ethyl]-7-glyoxylmethoxybenz-furan (IV) with isopropylamine (B) in ethanol gives the corresponding Schiff base (V), which is then reduced with NaBH4 and hydrolyzed with HCl in ethanol. 5) By hydrolysis of 3-isopropyl-5-(2-acetyl-7-benzofuryloxymethyl)oxazolidinone (VI) with aqueous refluxing NaOH. 6) By reaction of 2-acetyl-7-(2-hydroxy-3-aminopropoxy)benzofuran (VII) with isopropyl bromide (D) in ethanol at 100 C.

参考文献 中间体
合成目标
【1】 Ito, K.; Ikemoto, M.; Kimura, K.; Uchida, K.; Nakanishi, T.; JP 7436664 .
【2】 Ito, K.; Ikemoto, M.; Kimura, K.; Uchida, K.; Nakanishi, T.; JP 7442664 .
【3】 Ito, K.; Ikemoto, M.; Kimura, K.; Uchida, K.; Nakanishi, T.; JP 7441358 .
【4】 Ito, K.; Ikemoto, M.; Kimura, K.; Nakanishi, T.; JP 7443960 .
【5】 Ito, K.; Ikemoto, M.; Kimura, K.; Uchida, K.; Nakanishi, T.; JP 7443961 .
【6】 Ito, K.; Ikemoto, M.; Kimura, K.; Nakanishi, T. (Kaken Pharmaceutical Co., Ltd.); 2-Substittuted-(2-hydroxy-3-lower alkalinopropoxy)benzofurans. DE 2223184; FR 2137901; JP 7242747; US 3853923 .
【7】 Castaner, J.; Blancafort, P.; Weetman, D.F.; Serradell, M.N.; Befunolol. Drugs Fut 1981, 6, 10, 601.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(A) 10146 Epichlorohydrin; 2-(Chloromethyl)oxirane 106-89-8 C3H5ClO 详情 详情
(B) 23933 2-Propanamine; Isopropylamine 75-31-0 C3H9N 详情 详情
(D) 32658 2-bromopropane 75-26-3 C3H7Br 详情 详情
(I) 32291 1-(7-hydroxy-1-benzofuran-2-yl)-1-ethanone 40020-87-9 C10H8O3 详情 详情
(II) 32292 1-[7-(2-oxiranylmethoxy)-1-benzofuran-2-yl]-1-ethanone C13H12O4 详情 详情
(III) 32293 3-[[2-(2-methyl-1,3-dioxolan-2-yl)-1-benzofuran-7-yl]oxy]-2-oxopropanal oxime C15H15NO6 详情 详情
(IV) 32294 3-[[2-(2-methyl-1,3-dioxolan-2-yl)-1-benzofuran-7-yl]oxy]-2-oxopropanal C15H14O6 详情 详情
(V) 32295 1-(isopropylimino)-3-[[2-(2-methyl-1,3-dioxolan-2-yl)-1-benzofuran-7-yl]oxy]acetone C18H21NO5 详情 详情
(VI) 32296 5-[[(2-acetyl-1-benzofuran-7-yl)oxy]methyl]-3-isopropyl-1,3-oxazolidin-2-one C17H19NO5 详情 详情
(VII) 32297 1-[7-(3-amino-2-hydroxypropoxy)-1-benzofuran-2-yl]-1-ethanone C13H15NO4 详情 详情
(C) 32298 1-chloro-3-(isopropylamino)-2-propanol C6H14ClNO 详情 详情

合成路线17

该中间体在本合成路线中的序号：(VII)

This compound has been obtained by two related ways: 1) The reaction of phenol (I) with formaldehyde gives 4-(hydroxymethyl)phenol (II), which is treated with NaCN in hot DMF to yield 2-(4-hydroxyphenyl)acetonitrile (III). The hydrolysis of (III) in refluxing ethanol/water, catalyzed by a Pt catalyst affords the corresponding acetamide (IV), which is condensed with an excess of hot epichlorohydrin (V) by means of piperidine gives 2-[4-(2-oxiranylmethoxy)phenyl]acetamide (VI). Finally, the oxirane ring of (VI) is opened with isopropylamine in methanol. 2)The condensation of acetonitrile (III) with epichlorohydrin (V) as before gives the 2-[4-(2-oxiranylmethoxy)phenyl]acetonitrile (VIII), which is treated with isopropylamine (VII) in methanol yielding 2-[4-[2-hydroxy-3-(isopropylamino)propoxy]phenyl]acetonitrile (IX). Finally, this compound is hydrolyzed with refluxing ethanol/water catalyzed by a Pt catalyst as before to afford the target acetamide.

参考文献 中间体
合成目标
【1】 Akisanya, J.; et al.; A synthesis of atenolol using a nitrile hydration catalyst. Org Process Res Dev 1998, 2, 4, 274.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(I) 23540 Phenol 108-95-2 C6H6O 详情 详情
(II) 29474 4-(hydroxymethyl)phenol; 4-hydroxyphenylmethanol 4-hydroxybenzenemethanol; 4-Hydroxybenzyl alcohol 623-05-2 C7H8O2 详情 详情
(III) 32753 2-(4-hydroxyphenyl)acetonitrile; 4-Hydroxybenzyl cyanide 14191-95-8 C8H7NO 详情 详情
(IV) 32754 p-Hydroxyphenylacetamide; 2-(4-hydroxyphenyl)acetamide; 4-Hydroxybenzeneacetamide; 4-Hydroxyphenylacetamide 17194-82-0 C8H9NO2 详情 详情
(V) 10146 Epichlorohydrin; 2-(Chloromethyl)oxirane 106-89-8 C3H5ClO 详情 详情
(VI) 32755 2-[4-(2-oxiranylmethoxy)phenyl]acetamide C11H13NO3 详情 详情
(VII) 23933 2-Propanamine; Isopropylamine 75-31-0 C3H9N 详情 详情
(VIII) 32756 2-[4-(2-oxiranylmethoxy)phenyl]acetonitrile C11H11NO2 详情 详情
(IX) 32757 2-[4-[2-hydroxy-3-(isopropylamino)propoxy]phenyl]acetonitrile C14H20N2O2 详情 详情

合成路线18

该中间体在本合成路线中的序号：(IV)

Prepared in two steps by condensation of p-hydroxyphenylacetamide (I) and epichlorhydrine (II) with piperidine as catalyst, giving 1-(p-carbamoylmethylphenoxy)-2,3-epoxypropane (III), m.p. 158-60 C, followed by reaction of the epoxy ring with isopropylamine (IV).

参考文献 中间体
合成目标
【1】 Barret, A.; et al.; Alkanolaminderivate. CH 547257; CH 553747; DE 2007751; ES 376788; FR 2034561 .
【2】 Castaner, J.; Atenolol. Drugs Fut 1976, 1, 1, 7.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(I) 32754 p-Hydroxyphenylacetamide; 2-(4-hydroxyphenyl)acetamide; 4-Hydroxybenzeneacetamide; 4-Hydroxyphenylacetamide 17194-82-0 C8H9NO2 详情 详情
(II) 10146 Epichlorohydrin; 2-(Chloromethyl)oxirane 106-89-8 C3H5ClO 详情 详情
(III) 32755 2-[4-(2-oxiranylmethoxy)phenyl]acetamide C11H13NO3 详情 详情
(IV) 23933 2-Propanamine; Isopropylamine 75-31-0 C3H9N 详情 详情

合成路线19

该中间体在本合成路线中的序号：

Thermal cyclization of the azidocinnamate (II), obtained from O-benzylsalicylaldehyde (I) by methoxide condensation with ethyl azidoacetate, provides methyl 4-benzyloxyindol-2-carboxylate (III). Debenzylation by catalytic hydrogenolysis and alkylation of the phenol with (2S)-glycidyl tosylate gives the chiral oxirane (IV). Ring opening of (IV) followed by protection of the secondary amine by reaction with di-tert-butyldicarbonate and saponification of the methyl ester gives the key (S)-beta-blocker synthon (V). The required ACE inhibitor svnthon (VIII) is assembled from tert-butyl-N'-benzyloxycarbonyl-(S)-lysinate (VI). Alkylation of the alpha-amino group with the triflate of methyl (R)-lactate and saponification of the methyl ester gives N-[5-benzyloxycarbonylamino-1-(S)-tert-butyloxycarbonylpent-1-yl-(S)-alanine (VII). Condensation of (VII) with tert-butyl-(S)-prolinate. mediated by dicyclohexylcarbodiimide and 1-hydroxybenzotriazole, followed by hydrogenolytic removal of the benzyloxycarbonyl group, provides tert-butyl-N-[5-amino-1-(S)-tert-butyloxycarbonylpent-1-yl]-(S)-alanyl-(S)-prolinate (VIII). Coupling of (V) with (VIII) using dicyclohexylcarbodiimide-1-hydroxybenzotriazole and removal of the tert-butyl protecting groups by acidolysis in trifluoroacetic acid, with ethyl methyl sulfide as a scavenger, gives crude BW-8385C as the bistrifluoroacetate salt. Purification is achieved by ion exchange chromatography on DE52 cellulose, followed by reverse-phase desalting to provide pure BW-B385C as the zwitterionic trihydrate.

参考文献 中间体
合成目标
【1】 Allan, G.; Hardy, G.W.; BW-B385C. Drugs Fut 1988, 13, 3, 203.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
16242 (2R)oxiranylmethyl 4-methylbenzenesulfonate; (2R)-(-)-Glycidyl tosylate 113826-06-5 C10H12O4S 详情 详情
19832 tert-butyl (2S)-2-pyrrolidinecarboxylate C9H17NO2 详情 详情
23933 2-Propanamine; Isopropylamine 75-31-0 C3H9N 详情 详情
32916 ethyl 2-azidoacetate 637-81-0 C4H7N3O2 详情 详情
63428 3-methyl-1H-indole C9H9N 详情 详情
(I) 21874 2-(benzyloxy)benzaldehyde 5896-17-3 C14H12O2 详情 详情
(II) 21875 methyl (Z)-2-azido-3-[2-(benzyloxy)phenyl]-2-propenoate C17H15N3O3 详情 详情
(III) 21876 methyl 4-(benzyloxy)-1H-indole-2-carboxylate C17H15NO3 详情 详情
(IV) 21877 methyl 4-[(2R)oxiranylmethoxy]-1H-indole-2-carboxylate C13H13NO4 详情 详情
(V) 21878 4-([(2S)-3-[(tert-butoxycarbonyl)(isopropyl)amino]-2-hydroxypropyl]oxy)-1H-indole-2-carboxylic acid C20H28N2O6 详情 详情
(VI) 21879 tert-butyl (2S)-2-amino-6-[[(benzyloxy)carbonyl]amino]hexanoate C18H28N2O4 详情 详情
(VII) 21880 (2S)-2-[[(1S)-5-[[(benzyloxy)carbonyl]amino]-1-(tert-butoxycarbonyl)pentyl]amino]propionic acid C21H32N2O6 详情 详情
(VIII) 21881 tert-butyl (2S)-1-((2S)-2-[[(1S)-5-amino-1-(tert-butoxycarbonyl)pentyl]amino]propanoyl)-2-pyrrolidinecarboxylate C22H41N3O5 详情 详情
(IX) 21882 tert-butyl (2S)-1-((2S)-2-[[(1S)-1-(tert-butoxycarbonyl)-5-([[4-([(2S)-3-[(tert-butoxycarbonyl)(isopropyl)amino]-2-hydroxypropyl]oxy)-1H-indol-2-yl]carbonyl]amino)pentyl]amino]propanoyl)-2-pyrrolidinecarboxylate C42H67N5O10 详情 详情

合成路线20

该中间体在本合成路线中的序号：(VIII)

The condensation of 4-[2-(cyclopropylmethoxy)ethyl]phenol (I) with epichlorohydrin (II) in pyridine gives the phenol ether (III), which is treated with HCl to open the epoxide ring and yield the racemic chloropropanol (IV). The optical resolution of (IV) by means of Lipase SP 435-L or AK and vinyl acetate (V) gives a mixture of (S)-acetate (S)-(VI) and unreacted (R)-alcohol (R)-(VI) that is easily separated. Finally, the chiral chloropropanol (R)-(VI) is treated with isopropylamine (VII) to afford the target betaxolol. The optical resolution of racemic betaxolol by means of the previously mentioned lipases has also been tried with poor results.

参考文献 中间体
合成目标
【1】 Di Bono, G.; Scilimati, A.; Synthesis 1995, 6, 688.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(I) 33330 4-[2-(Cyclopropylmethoxy)ethyl]phenol; p-(Cyclopropylmethoxyethyl)phenol C12H16O2 详情 详情
(II) 10146 Epichlorohydrin; 2-(Chloromethyl)oxirane 106-89-8 C3H5ClO 详情 详情
(III) 33331 2-([4-[2-(Cyclopropylmethoxy)ethyl]phenoxy]methyl)oxirane; 1-[p-(Cyclopropylmethoxyethyl)phenoxy]-2,3-epoxypropane; 4-[2-(Cyclopropylmethoxy)ethyl]phenyl 2-oxiranylmethyl ether C15H20O3 详情 详情
(IV) 55675 1-chloro-3-{4-[2-(cyclopropylmethoxy)ethyl]phenoxy}-2-propanol C15H21ClO3 详情 详情
(V) 24543 vinyl acetate 108-05-4 C4H6O2 详情 详情
(VI) 55676 (2R)-1-chloro-3-{4-[2-(cyclopropylmethoxy)ethyl]phenoxy}-2-propanol C15H21ClO3 详情 详情
(VII) 55676 (2R)-1-chloro-3-{4-[2-(cyclopropylmethoxy)ethyl]phenoxy}-2-propanol C15H21ClO3 详情 详情
(VIII) 23933 2-Propanamine; Isopropylamine 75-31-0 C3H9N 详情 详情

合成路线21

该中间体在本合成路线中的序号：(V)

Condensation of acetamide (I) with (R)-epichlorohydrin (II) by means of either NaOH, LiOH or NaOH/benzyltrimethylammonium chloride (BTA-Cl) in H2O yields a mixture of epoxypropane (III) and chloropropanol derivative (IV) that can be converted into the desired product either by direct coupling with isopropylamine (V) in MeOH, or by first reaction of the mixture (III)/(IV) with NaOH to give (S)-(III) and next coupling with (V) as described above (1-3). Alternatively, derivative (S)-(III) can also be obtained by coupling of glycidyl nosylate (VI) with acetamide (I) by means of CsF in DMF.

参考文献 中间体
合成目标
【1】 Kitaori, K.; et al.; A practical synthesis of optically active atenolol from chiral epichlorohydrin. Chem Pharm Bull 1997, 45, 2, 412.
【2】 Kitaori, K.; et al.; CsF in organic synthesis. Regioselective nucleophilic reactions of phenols with oxiranes leading to enantiopure beta-blockers. Tetrahedron 1999, 55, 50, 14381.
【3】 Kitaori, K.; et al.; Convenient preparation of enantiopure atenolol by means of preferential crystallization. Chem Pharm Bull 1998, 46, 3, 505.
【4】 Saragai, N.; Takehira, Y.; Kitaori, K. (Daiso Co., Ltd.); Process for producing optically active atenolol and intermediate thereof. EP 0435068 .
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(S)-(III) 51074 2-[4-[(2S)oxiranylmethoxy]phenyl]acetamide C11H13NO3 详情 详情
(I) 32754 p-Hydroxyphenylacetamide; 2-(4-hydroxyphenyl)acetamide; 4-Hydroxybenzeneacetamide; 4-Hydroxyphenylacetamide 17194-82-0 C8H9NO2 详情 详情
(II) 38067 (2R)-2-(Chloromethyl)oxirane; (R)-Epichlorohydrin 51594-55-9 C3H5ClO 详情 详情
(III) 51072 2-[4-[oxiranylmethoxy]phenyl]acetamide C11H13NO3 详情 详情
(IV) 51073 2-(4-[[(2R)-3-chloro-2-hydroxypropyl]oxy]phenyl)acetamide C11H14ClNO3 详情 详情
(V) 23933 2-Propanamine; Isopropylamine 75-31-0 C3H9N 详情 详情
(VI) 45631 (2S)oxiranylmethyl 4-nitrobenzenesulfonate C9H9NO6S 详情 详情

合成路线22

该中间体在本合成路线中的序号：(X)

Esterification of p-hydroxyphenylacetic acid (I) with NaHSO4 in refluxing butanol provides butyl acetate derivative (II), which is then subjected to reaction with epichlorohydrin (III) in pyridine to furnish a mixture of epoxypropane (IV) and chloro derivative (V). Treatment of the mixture (IV)/(V) with HCl affords derivative (VI), which is then selectively acylated by means of Lipase Amano PS (LAPS) and vinyl acetate or acetic anhydride/diisopropyl ether to yield compound (S)-(VII). Treatment of the mixture (IV)/(V) with acetyl chloride gives derivative (VIII), which is selectively deacylated using LAPS in butanol/diisopropyl ether to afford derivative (S)-(IX). Coupling of derivative (S)-(VII) with isopropylamine (X) in H2O, followed by removal of the acetyl group with NaOH furnishes derivative (XI) (alternatively, (XI) can also be synthesized by coupling of (S)-(IX) with amine (X)). Finally, conversion of (XI) into the desired product is achieved by treatment with ammonium hydroxide in MeOH.

参考文献 中间体
合成目标
【1】 Banerji, A.A.; Bevinakatti, H.S.; Lipase catalysis in organic solvents. Application to the synthesis of (R)- and (S)-atenolol. J Org Chem 1992, 57, 22, 6003.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(V),(VI) 51078 butyl 2-[4-(3-chloro-2-hydroxypropoxy)phenyl]acetate C15H21ClO4 详情 详情
(S)-(VII) 51079 butyl 2-(4-[[(2R)-2-(acetoxy)-3-chloropropyl]oxy]phenyl)acetate C17H23ClO5 详情 详情
(S)-(IX) 51080 butyl 2-(4-[[(2R)-3-chloro-2-hydroxypropyl]oxy]phenyl)acetate C15H21ClO4 详情 详情
(I) 18430 2-(4-Hydroxyphenyl)acetic acid; 4-Hydroxyphenylacetic acid 156-38-7 C8H8O3 详情 详情
(II) 51075 butyl 2-(4-hydroxyphenyl)acetate C12H16O3 详情 详情
(III) 10146 Epichlorohydrin; 2-(Chloromethyl)oxirane 106-89-8 C3H5ClO 详情 详情
(IV) 51077 butyl 2-[4-(2-oxiranylmethoxy)phenyl]acetate C15H20O4 详情 详情
(VIII) 51082 butyl 2-[4-[2-(acetoxy)-3-chloropropoxy]phenyl]acetate C17H23ClO5 详情 详情
(X) 23933 2-Propanamine; Isopropylamine 75-31-0 C3H9N 详情 详情
(XI) 51081 butyl 2-(4-[[(2S)-2-hydroxy-3-(isopropylamino)propyl]oxy]phenyl)acetate C18H29NO4 详情 详情

合成路线23

该中间体在本合成路线中的序号：(V)

Treatment of sodium phenoxide derivative (I) with Amberlite IRA-400 (containing quaternary ammonium groups) provides resin (II), which is then coupled with epichlorohydrin (III) in refluxing MeOH to afford arylepoxyether (IV). Finally, (S)-atenolol is obtained by reaction of (IV) with isopropylamine (V) in refluxing MeOH.

参考文献 中间体
合成目标
【1】 Damle, S.V.; et al.; One pot synthesis of (±)/(S)-atenolol and (±)/(S)-propranolol by employing polymer supported reagent. Synth Commun 1999, 29, 10, 1639.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(I) 51083 sodium 4-(2-amino-2-oxoethyl)benzenolate C8H8NNaO2 详情 详情
(II) 51084 N,N,N-trimethylmethanaminium 4-(2-amino-2-oxoethyl)benzenolate C12H20N2O2 详情 详情
(III) 38067 (2R)-2-(Chloromethyl)oxirane; (R)-Epichlorohydrin 51594-55-9 C3H5ClO 详情 详情
(IV) 51072 2-[4-[oxiranylmethoxy]phenyl]acetamide C11H13NO3 详情 详情
(V) 23933 2-Propanamine; Isopropylamine 75-31-0 C3H9N 详情 详情

合成路线24

该中间体在本合成路线中的序号：(III)

In this scheme various methods are shown for the synthesis of (S)-atenolol: 1. Treatment of (R)-glycidyl 4-nitrobenzenesulfonate (I) with HCl (either concentrated or with dichloromethane) provides 3-chloropropyl derivative (II), which is then coupled with isopropylamine (III) in dichloromethane to afford 3-chloropropylisopropylamine (IV). Finally, condensation of (IV) with 2-(4-hydroxyphenyl)acetamide (V) by means of KOH in MeOH gives the desired product. Alternatively, derivative (IV) can be converted into (S)-atenolol by its condensation with 2-(4-hydroxy-phenyl)acetonitrile (VI) by means of KOH to yield compound (VII), followed by hydrolysis with HCl at 40 C. 2. Condensation of (R)-glycidyl 3-nitrobenzenesulfonate (VIII) with isopropylamine (III) followed by coupling with acetamide (V) by means of potassium tert-butylate in DMSO provides the desired product. 3. Treatment of (VIII) with HCl affords 2(S)-hydroxy-3-chloropropyl-3-nitrobenzenesulfonate (IX), which is first coupled with isopropylamine (III) to give (IV) and finally condensed with amide (V). 4. Coupling of chloro derivative (IX) with benzyl-protected isopropylamine (X) provides protected derivative (XI), which is then condensed with acetamide (V) by means of KOH in MeOH to give (XII). Finally, compound (XII) is hydrogenated over Pd/C in MeOH for removal of the benzyl group.

参考文献 中间体
合成目标
【1】 Westfelt, A.; Andersson, L.; Birgersson, B.; Westfelt, L.; Process for preparing homochiral amines and process for preparing intermediates for the preparation thereof, and the intermediates prepared in accordance with this process. WO 9110642 .
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(I) 45631 (2S)oxiranylmethyl 4-nitrobenzenesulfonate C9H9NO6S 详情 详情
(II) 51089 (2S)-3-chloro-2-hydroxypropyl 4-nitrobenzenesulfonate C9H10ClNO6S 详情 详情
(III) 23933 2-Propanamine; Isopropylamine 75-31-0 C3H9N 详情 详情
(IV) 51090 (2S)-1-chloro-3-(isopropylamino)-2-propanol C6H14ClNO 详情 详情
(V) 32754 p-Hydroxyphenylacetamide; 2-(4-hydroxyphenyl)acetamide; 4-Hydroxybenzeneacetamide; 4-Hydroxyphenylacetamide 17194-82-0 C8H9NO2 详情 详情
(VI) 32753 2-(4-hydroxyphenyl)acetonitrile; 4-Hydroxybenzyl cyanide 14191-95-8 C8H7NO 详情 详情
(VII) 51088 2-(4-[[(2S)-2-hydroxy-3-(isopropylamino)propyl]oxy]phenyl)acetonitrile C14H20N2O2 详情 详情
(VIII) 16259 (2S)oxiranylmethyl 3-nitrobenzenesulfonate; (S)-(+)-Glycidyl nosylate 115314-14-2 C9H9NO6S 详情 详情
(IX) 51091 (2S)-3-chloro-2-hydroxypropyl 3-nitrobenzenesulfonate C9H10ClNO6S 详情 详情
(X) 39750 N-benzyl-N-isopropylamine; N-benzyl-2-propanamine 102-97-6 C10H15N 详情 详情
(XI) 51092 (2S)-1-[benzyl(isopropyl)amino]-3-chloro-2-propanol C13H20ClNO 详情 详情
(XII) 51093 2-[4-([(2S)-3-[benzyl(isopropyl)amino]-2-hydroxypropyl]oxy)phenyl]acetamide C21H28N2O3 详情 详情

合成路线25

该中间体在本合成路线中的序号：(VII)

The title compound can be obtained by several synthetic procedures. Esterification of the thiophenecarboxylic acid (I) with simultaneous N-t-butyl group cleavage in ethanolic HCl affords (II). Ethyl ester (II) is then converted to hydrazide (III) with hydrazine hydrate. Reaction of (III) with NaNO2/HCl leads to the acyl azide (IV), which is subsequently subjected to Curtius rearrangement in boiling toluene to produce the thienothiadiazine derivative (V). Condensation of (V) with isopropylamine (VII) by heating with P2O5 furnishes the target compound in low yield. In an improved method, chlorination of (V) in the presence of POCl3 leads to (VI), which is further reacted with isopropylamine (VII) to afford the title compound

参考文献 中间体
合成目标
【1】 Nielsen, F.E.; Bodvarsdottir, T.B.; Worsaae, A.; et al.; 6-Chloro-3-alkylamino-4H-thieno[3,2-e]-1,2,4-thiadiazine 1,1-dioxide derivatives potently and selectively activate ATP sensitive potassium channels of pancreatic beta-cells. J. Med. Chem. 2002, 45, 19, 4171.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(I) 61482 2-[(tert-butylamino)sulfonyl]-5-chloro-3-thiophenecarboxylic acid C9H12ClNO4S2 详情 详情
(II) 61483 ethyl 2-(aminosulfonyl)-5-chloro-3-thiophenecarboxylate C7H8ClNO4S2 详情 详情
(III) 61484 5-chloro-3-(hydrazinocarbonyl)-2-thiophenesulfonamide C5H6ClN3O3S2 详情 详情
(IV) 61485 2-(aminosulfonyl)-5-chloro-3-thiophenecarbonyl azide C5H3ClN4O3S2 详情 详情
(V) 61486 6-chloro-1lambda~6~-thieno[3,2-e][1,2,4]thiadiazine-1,1,3(2H,4H)-trione C5H3ClN2O3S2 详情 详情
(VI) 56052 3,6-dichloro-1lambda~6~-thieno[3,2-e][1,2,4]thiadiazine-1,1(4H)-dione C5H2Cl2N2O2S2 详情 详情
(VII) 23933 2-Propanamine; Isopropylamine 75-31-0 C3H9N 详情 详情

合成路线26

该中间体在本合成路线中的序号：(IV)

Alkylation of 4-[2,3-dinitroxy)propoxymethyl]phenol (I) with epichlorhydrin (II) in the presence of NaOH provided the corresponding epoxypropoxy derivative (III). Then, epoxide opening with isopropylamine (IV) in refluxing MeOH furnished the desired amino alcohol.

参考文献 中间体
合成目标
【1】 Prat Quinones, M.; Pi Sallent, J.; Vedrilla Veit, D. (Almirall Prodesfarma, SA); 1-Aryloxy-3-alkylamino-2-propanol nitrate esters, the use thereof and corresponding pharmaceutical compsn.. EP 0637583; JP 1995089910 .
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(I) 36607 4-[[2,3-bis(nitrooxy)propoxy]methyl]phenol C10H12N2O8 详情 详情
(II) 10146 Epichlorohydrin; 2-(Chloromethyl)oxirane 106-89-8 C3H5ClO 详情 详情
(III) 36608 2-[(4-[[2,3-bis(nitrooxy)propoxy]methyl]phenoxy)methyl]oxirane; 4-[[2,3-bis(nitrooxy)propoxy]methyl]phenyl 2-oxiranylmethyl ether C13H16N2O9 详情 详情
(IV) 23933 2-Propanamine; Isopropylamine 75-31-0 C3H9N 详情 详情

合成路线27

该中间体在本合成路线中的序号：(II)

Reductive amination of pyridine-4-carbaldehyde (I) with isopropylamine (II) in the presence of NaBH4 furnished the secondary amine (III). This was then acylated with the indoleacetic acid (IV) using PyBOP as the coupling reagent to yield the target amide.

参考文献 中间体
合成目标
【1】 Lumma, W.C.; Quigley, A.G.; Sisko, J.T.; et al.; 2-Arylindole-3-acetamides as FPP-competitive inhibitors of farnesyltransferase. 221st ACS Natl Meet (April 1 2001, San Diego) 2001, Abst MEDI 154.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(I) 17203 4-Pyridinecarboxaldehyde; isonicotinaldehyde 872-85-5 C6H5NO 详情 详情
(II) 23933 2-Propanamine; Isopropylamine 75-31-0 C3H9N 详情 详情
(III) 50896 N-isopropyl-N-(4-pyridinylmethyl)amine; N-(4-pyridinylmethyl)-2-propanamine C9H14N2 详情 详情
(IV) 50897 2-(1-methyl-2-phenyl-1H-indol-3-yl)acetic acid C17H15NO2 详情 详情

合成路线28

该中间体在本合成路线中的序号：(VI)

The acetylation of 4-acetamidophenol (I) with acetyl chloride in refluxing benzene gives 4-acetoxyacetanilide (II), which by a Fries reaction with AlCl3 at 170 C is converted into 2-hydroxy-5-acetamidoacetophenone (III). (1,2) The reaction of (III) with epichlorohydrin (IV) by means of sodium ethoxide in refluxing ethanol affords 1-(2-acetyl-4-acetamidophenoxy)-2,3-epoxypropane (V), which is finally treated with isopropylamine (VI) in refluxing ethanol. (1-3)

参考文献 中间体
合成目标
【1】 Woolbridge, K.R.H.; Basil, B (May & Baker, Ltd.); ZA 6808345 .
【2】 Basil, B.; et al.; New series of cardioselective adrenergic beta-receptor blocking compounds. 1-(2-Acyl-4-acylaminophenoxy)3-isopropylaminopropan-2-ols. J Med Chem 1976, 19, 3, 399.
【3】 Woolbridge, K.R.H.; Basil, B. (May & Baker, Ltd.); BE 715205; CA 834734; CH 485663; CH 489467; FR 1570087; FR M7616; GB 1231783; GB 681537; JP 7134414; NL 6806946; ZA 6803130 .
【4】 Blancafort, P.; Serradell, M.N.; Castaner, J.; Weetman, D.F.; Diacetolol hydrochloride. Drugs Fut 1981, 6, 8, 467.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(I) 21611 4'-Hydroxyacetanilide;4-Acetamidophenol;N-Acetyl-4-aminophenol;Paracetamol;Acetaminophen;p-Hydroxyacetanilide; Paracetamol; N-(4-hydroxyphenyl)acetamide 103-90-2 C8H9NO2 详情 详情
(II) 60980 4-(acetylamino)phenyl acetate C10H11NO3 详情 详情
(III) 21612 N-(3-acetyl-4-hydroxyphenyl)acetamide C10H11NO3 详情 详情
(IV) 10146 Epichlorohydrin; 2-(Chloromethyl)oxirane 106-89-8 C3H5ClO 详情 详情
(V) 60981 N-[3-acetyl-4-(2-oxiranylmethoxy)phenyl]acetamide C13H15NO4 详情 详情
(VI) 23933 2-Propanamine; Isopropylamine 75-31-0 C3H9N 详情 详情

合成路线29

该中间体在本合成路线中的序号：(IV)

The condensation of o-(methylthio)phenol (I) with epichlorohydrin (II) by means of sodium hydroxide in water gives 3-[o-(methylthio)phenoxy]-1,2-epoxypropane (III), which is then treated with isopropylamine (IV) in hot water and finally with ethanolic HCl

参考文献 中间体
合成目标
【1】 (N.V. Philips' Gloeilampenfabrieken); BE 679005; CA 832495; DE 1543790; FR 1552786; FR 6393; GB 1137764; JP 6902978; NL 6504268; US 3542874; US 3632780 .
【2】 Blancafort, P.; Serradell, M.N.; Castaner, J.; Weetman, D.F.; Tiprenolol hydrochloride. Drugs Fut 1979, 4, 11, 830.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(I) 28075 2-(methylsulfanyl)phenol 1073-29-6 C7H8OS 详情 详情
(II) 10146 Epichlorohydrin; 2-(Chloromethyl)oxirane 106-89-8 C3H5ClO 详情 详情
(III) 60944 2-(methylsulfanyl)phenyl 2-oxiranylmethyl ether; 2-{[2-(methylsulfanyl)phenoxy]methyl}oxirane C10H12O2S 详情 详情
(IV) 23933 2-Propanamine; Isopropylamine 75-31-0 C3H9N 详情 详情
(V) 60945 1-(isopropylamino)-3-[2-(methylsulfanyl)phenoxy]-2-propanol C13H21NO2S 详情 详情

合成路线30

该中间体在本合成路线中的序号：(IX)

The reaction of 3,4-dichlorophenol (I) with 1,3-dibromopropane (II) by means of NaOH and tetrabutylammonium hydrogensulfate gives the corresponding phenol ether (III), which is condensed with N-acetylhydroxylamine (IV) by means of NaOH or KOH in an alcoholic solvent to yield the O-substituted acetylhydroxylamine (V). The hydrolysis of (V) with HCl in methanol affords the free O-substituted hydroxylamine (VI), which is finally condensed with N1-cyano-N3-isopropylguanidine (VII) in hot ethyl acetate. The intermediate N1-cyano-N3-isopropylguanidine (VII) has been obtained by reaction of sodium dicyanamide (VIII) with isopropylamine (IX) and HCl in a hot alcoholic solvent.

参考文献 中间体
合成目标
【1】 Jensen, N.P.; et al.; Phenoxypropoxybiguanides, prodrugs of DHFR-inhibiting diaminotriazine antimalarials. J Med Chem 2001, 44, 23, 3925.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(I) 34044 3,4-Dichlorophenol 95-77-2 C6H4Cl2O 详情 详情
(II) 12581 1,3-Dibromopropane 109-64-8 C3H6Br2 详情 详情
(III) 52210 3-bromopropyl 3,4-dichlorophenyl ether; 4-(3-bromopropoxy)-1,2-dichlorobenzene C9H9BrCl2O 详情 详情
(IV) 23102 N-hydroxyacetamide 546-88-3 C2H5NO2 详情 详情
(V) 52211 N-[3-(3,4-dichlorophenoxy)propoxy]acetamide C11H13Cl2NO3 详情 详情
(VI) 52212 4-[3-(aminooxy)propoxy]-1,2-dichlorobenzene; O-[3-(3,4-dichlorophenoxy)propyl]hydroxylamine C9H11Cl2NO2 详情 详情
(VII) 52213 N-cyano-N'-isopropylguanidine C5H10N4 详情 详情
(VIII) 52214 　 C2N3Na 详情 详情
(IX) 23933 2-Propanamine; Isopropylamine 75-31-0 C3H9N 详情 详情

合成路线31

该中间体在本合成路线中的序号：(IV)

The reaction of dibenzazepine (I) with the chiral epichlorohydrin (II) by means of NaNH2 in refluxing benzene gives the adduct (III), which is finally treated with isopropylamine (IV) to yield the target isopropanol derivative.

参考文献 中间体
合成目标
【1】 Levy, O.; et al.; A new class of antiarrhythmic-defibrillatory agents. Bioorg Med Chem Lett 2001, 11, 22, 2921.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(I) 37265 4'-(hydroxymethyl)[1,1'-biphenyl]-2-carbonitrile C14H11NO 详情 详情
(II) 38067 (2R)-2-(Chloromethyl)oxirane; (R)-Epichlorohydrin 51594-55-9 C3H5ClO 详情 详情
(III) 54451 5-[(2R)oxiranylmethyl]-10,11-dihydro-5H-dibenzo[b,f]azepine C17H17NO 详情 详情
(IV) 23933 2-Propanamine; Isopropylamine 75-31-0 C3H9N 详情 详情

合成路线32

该中间体在本合成路线中的序号：(II)

The reaction of 6-(2,6-difluorobenzyl)-5-methyl-2-(methylsulfanyl)pyrimidin-4(3H)-one (I) with isopropylamine (II) gives the target aminopyrimidinone.

参考文献 中间体
合成目标
【1】 Artico, M.; Selected non-nucleoside reverse transcriptase inhibitors (NNRTIs): the DABOs family. Drugs Fut 2002, 27, 2, 159.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(I) 51828 6-(2,6-difluorobenzyl)-5-methyl-2-(methylsulfanyl)-4(3H)-pyrimidinone C13H12F2N2OS 详情 详情
(II) 23933 2-Propanamine; Isopropylamine 75-31-0 C3H9N 详情 详情

合成路线33

该中间体在本合成路线中的序号：(II)

The condensation of the epoxide (I) with isopropylamine (II) gives the target isopropanol derivative.

参考文献 中间体
合成目标
【1】 Zolss, G.; Pfarrhofer, G. (Aventis Pharma AG); Novel crystalline salts of aryloxy-propanolamines, a process for their preparation and their use. DE 3544172; EP 0229947; US 4767784 .
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(I) 62420 2,3,6-trimethyl-4-(2-oxiranylmethoxy)phenyl acetate C14H18O4 详情 详情
(II) 23933 2-Propanamine; Isopropylamine 75-31-0 C3H9N 详情 详情

合成路线34

该中间体在本合成路线中的序号：(V)

Alkylation of the sodium derivative of 1,2-ethylene dicysteine (I) with benzyl chloride in liquid ammonia affords the S,S'-dibenzyl compound (II). Subsequent protection of the amino groups of (II) with benzyl chloroformate provides the bis-carbamate (III). Esterification of diacid (III) with one equivalent of MeOH in the presence of DCC and DMAP furnishes the mono-methyl ester (IV). This is then coupled with 1-aminomethylenediphosphonic acid tetraethyl ester (V) to yield amide (VI). The ethyl phosphonate ester groups of (VI) are selectively cleaved by means of trimethylsilyl bromide, producing diphosphonic acid (VII). Further hydrolysis of the methyl carboxylate ester group of (VII) under basic conditions leads to acid (VIII). Then, simultaneous removal of the S-benzyl and N-Cbz protecting groups of (VIII) is accomplished by means of Na in liquid ammonia to furnish dithiol (IX). This is finally complexed with [99mTc] sodium pertechnetate in the presence of SnCl2 to produce the target technetium conjugate.

参考文献 中间体
合成目标
【1】 Verbeke, K.; et al.; Development of a conjugate of 99mTc-EC with aminomethylenediphosphonate in the search for a bone tracer with fast clearance from soft tissue. Bioconjugate Chem 2002, 13, 1, 16.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(I) 12945 (2R)-2-[(2-[[(1R)-1-Carboxy-2-sulfanylethyl]amino]ethyl)amino]-3-sulfanylpropionic acid C8H16N2O4S2 详情 详情
(II) 61689 (2R)-3-(benzylsulfanyl)-2-[(2-{[(1R)-2-(benzylsulfanyl)-1-carboxyethyl]amino}ethyl)amino]propanoic acid C22H28N2O4S2 详情 详情
(III) 61690 (2R)-2-[[(benzyloxy)carbonyl](2-{[(benzyloxy)carbonyl][(1R)-2-(benzylsulfanyl)-1-carboxyethyl]amino}ethyl)amino]-3-(benzylsulfanyl)propanoic acid C38H40N2O8S2 详情 详情
(IV) 61691 (2R)-2-{[(benzyloxy)carbonyl][2-([(benzyloxy)carbonyl]{(1R)-1-[(benzylsulfanyl)methyl]-2-methoxy-2-oxoethyl}amino)ethyl]amino}-3-(benzylsulfanyl)propanoic acid C39H42N2O8S2 详情 详情
(V) 23933 2-Propanamine; Isopropylamine 75-31-0 C3H9N 详情 详情
(VI) 61692 methyl (8R,13R)-9,12-bis[(benzyloxy)carbonyl]-8,13-bis[(benzylsulfanyl)methyl]-5-(diethoxyphosphoryl)-4-ethoxy-4,7-dioxo-3-oxa-6,9,12-triaza-4lambda~5~-phosphatetradecan-14-oate C48H63N3O13P2S2 详情 详情
(VII) 61693 (4R,9R)-5,8-bis[(benzyloxy)carbonyl]-4,9-bis[(benzylsulfanyl)methyl]-3,10-dioxo-1-phosphono-11-oxa-2,5,8-triazadodec-1-ylphosphonic acid C40H47N3O13P2S2 详情 详情
(VIII) 61694 (5R,10R)-6,9-bis[(benzyloxy)carbonyl]-5,10-bis[(benzylsulfanyl)methyl]-1,1-dihydroxy-1,4-dioxo-2-phosphono-3,6,9-triaza-1lambda~5~-phosphaundecan-11-oic acid C39H45N3O13P2S2 详情 详情
(IX) 61695 (5R,10R)-1,1-dioxido-1,4-dioxo-2-phosphonato-5,10-bis(sulfidomethyl)-3,6,9-triaza-1lambda~5~-phosphaundecan-11-oate C9H14N3O9P2S2 详情 详情

合成路线35

该中间体在本合成路线中的序号：(II)

The target thiadiazine dioxide has been obtained by reaction of 7-methoxy--3-(methylsulfanyl)-4H-1,2,4-benzothiadiazine-1,1-dioxide (I) or 3-(1-imidazolyl)-7-methoxy-4H-1,2,4-benzothiadiazine-1,1-dioxide (II) with isopropylamine (III) at 120-150 C in a pressure vessel.

参考文献 中间体
合成目标
【1】 Pirotte, B.; Lebrun, P.; De Tullio, P.; Somers, F.; Delarge, J.; Hansen, J.B.; Nielsen, F.E.; Hansen, H.C.; Mogensen, J.P.; Tagmose, T.M. (Novo Nordisk A/S); 1,2,4-Benzothiadiazine derivs. their preparation and use. EP 0906297; JP 2000512641; US 6242443; WO 9749692 .
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(I) 57156 7-methoxy-3-(methylsulfanyl)-1lambda~6~,2,4-benzothiadiazine-1,1(4H)-dione C9H10N2O3S2 详情 详情
(II) 23933 2-Propanamine; Isopropylamine 75-31-0 C3H9N 详情 详情
(III) 57157 3-(1H-imidazol-1-yl)-7-methoxy-1lambda~6~,2,4-benzothiadiazine-1,1(4H)-dione C11H10N4O3S 详情 详情
Extended Information