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【结 构 式】

【分子编号】12034

【品名】4-Chlorophenylamine; 4-Chloroaniline; p-Chloroaniline

【CA登记号】106-47-8

【 分 子 式 】C6H6ClN

【 分 子 量 】127.57308

【元素组成】C 56.49% H 4.74% Cl 27.79% N 10.98%
与该中间体有关的原料药合成路线共 20 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1

该中间体在本合成路线中的序号：(E)

Compound can be prepared in several different ways, all starting from 3,4-diethyl-DELTA2-1,2,4-triazolin-5-one (I): 1) The condensation of (I) with N-(3-bromopropyl)-N'-(m-chlorophenyl)piperazine (B) by means of NaNH2, NaH or sodium alcoholate in an organic solvent (DMSO, DMF, dioxane, benzene, alcohol, tetralin, etc.). 2) The condensation of (I) with 1-chloro-3-bromopropane (A) by means of sodium alcoholate in alcohol gives 1-(3-chloropropyl)-3,4-diethyl-DELTA2-1,2,4-triazolin-5-one (II), which is then condensed with an inert solvent by means of HCl acceptor. 3) The condensation of (II) with diethanolamine (C) affords 1-(3-bishydroxyethylaminopropyl)-3,4-diethyl-DELTA2-1,2,4-triazolin-5-one (III), which is then converted into the corresponding dichlorocompound (IV) by means of SOCl2. Finally, (IV) is cyclized with m-chloroaniline (E).

参考文献 中间体
合成目标
【1】 Palazzo, G.; 1-[3-(4-Metrachlorophenyl-1-piperazinyl)propyl]-3,4-diethyl-delta2-1,2,4-triazolin-5-one. DE 2351739; FR 2202702; GB 1438337; US 3857845 .
【2】 de Angelis, L.; Castaner, J.; Etoperidone. Drugs Fut 1977, 2, 3, 164.
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) 10358 1-Bromo-3-chloropropane 109-70-6 C3H6BrCl 详情 详情
(E) 12034 4-Chlorophenylamine; 4-Chloroaniline; p-Chloroaniline 106-47-8 C6H6ClN 详情 详情
(D) 24273 2-[(2-hydroxyethyl)amino]-1-ethanol 111-42-2 C4H11NO2 详情 详情
(B) 33592 1-(3-bromopropyl)-4-(4-chlorophenyl)piperazine C13H18BrClN2 详情 详情
(I) 33588 4,5-diethyl-2,4-dihydro-3H-1,2,4-triazol-3-one 52883-26-8 C6H11N3O 详情 详情
(II) 33589 2-(3-chloropropyl)-4,5-diethyl-2,4-dihydro-3H-1,2,4-triazol-3-one C9H16ClN3O 详情 详情
(III) 33591 2-[3-[bis(2-hydroxyethyl)amino]propyl]-4,5-diethyl-2,4-dihydro-3H-1,2,4-triazol-3-one C13H26N4O3 详情 详情
(IV) 33590 2-[3-[bis(2-chloroethyl)amino]propyl]-4,5-diethyl-2,4-dihydro-3H-1,2,4-triazol-3-one C13H24Cl2N4O 详情 详情
(C) 33593 1-(4-chlorophenyl)piperazine 38869-46-4 C10H13ClN2 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 alkylation of p-chloroaniline (V) as before yields N-(2,2,2-trifluoroethyl)aniline (VI), which is then condensed with aziridine (C) affording the substituted aniline (VII). The benzoylation of (VII) with 2-fluorobenzoyl chloride (D) yields the amide (VIII), which is cyclized with P2O5 in refluxing POCl3 giving 7-chloro-(2,2,2-trifluoroethyl)-1,3-dihydro-2H-5-(2-fluorophenyl)-1,4-benzodiazepine (IX). This compound is oxidized with RuO4 in CCl4 to give 7-chloro-1-(2,2,2-trifluoroethyl)-1,3-dihydro-5-(2-fluorophenyl)-2H-1,4-benzodiazepin-2-one (I), which by reaction with P2S5 in refluxing dioxane gives the target compound.

参考文献 中间体
合成目标
【1】 Steinman, M.; Benzodiazepines and the process for their manufacture. DE 2138773; ES 393953; FR 2102114; GB 1345938 .
【2】 Steinman, M.; 1-Polyfluoroalkyl-1,4-benzodiazepin-2-thiones for effecting tranquilization, sedation and treating colvulsions. US 3920818 .
【3】 Castaner, J.; Thorpe, P.; Quazepam. Drugs Fut 1978, 3, 2, 139.
【4】 Topliss, J.G.; Steinman, M.; Alekel, R.; Wong, Y.S.; York, E.E.; 1-Polyfluoroalkylbenzodiazepines. J Med Chem 1973, 16, 12, 1354-60.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(D) 19551 2-Fluorobenzoyl chloride 393-52-2 C7H4ClFO 详情 详情
(A) 33474 2,2,2-Trifluoroethyl trichloromethanesulfonate; 2,2,2-Trifluoroethyl trichloromethylsulfonate 23199-56-6 C3H2Cl3F3O3S 详情 详情
(I) 33471 7-Chloro-5-(2-fluorophenyl)-1-(2,2,2-trifluoroethyl)-1,3-dihydro-2H-1,4-benzodiazepin-2-one C17H11ClF4N2O 详情 详情
(V) 12034 4-Chlorophenylamine; 4-Chloroaniline; p-Chloroaniline 106-47-8 C6H6ClN 详情 详情
(VI) 33475 N-(4-chlorophenyl)-N-(2,2,2-trifluoroethyl)amine; 4-chloro-N-(2,2,2-trifluoroethyl)aniline C8H7ClF3N 详情 详情
(VII) 33476 N(1)-(4-chlorophenyl)-N(1)-(2,2,2-trifluoroethyl)-1,2-ethanediamine; N-(2-aminoethyl)-N-(4-chlorophenyl)-N-(2,2,2-trifluoroethyl)amine C10H12ClF3N2 详情 详情
(VIII) 33477 N-[2-[4-chloro(2,2,2-trifluoroethyl)anilino]ethyl]-2-fluorobenzamide C17H15ClF4N2O 详情 详情
(IX) 33478 7-chloro-5-(2-fluorophenyl)-1-(2,2,2-trifluoroethyl)-2,3-dihydro-1H-1,4-benzodiazepine; 7-chloro-(2,2,2-trifluoroethyl)-1,3-dihydro-2H-5-(2-fluorophenyl)-1,4-benzodiazepine C17H13ClF4N2 详情 详情
(C) 10151 Ethyleneimine; Aziridine; Azirane 151-56-4 C2H5N 详情 详情

合成路线3

该中间体在本合成路线中的序号：(IX)

The condensation of aniline (I) with diethyl ethoxymethylenemalonate (II) by heating at 90 C gives diethyl anilinomethylenemalonate (III), which is cyclized to ethyl 4-hydroxyquinoline-3carboxylate (IV) by heating at 240 C in diphenyl ether-biphenyl. The reaction of (IV) with hot POCl3 affords ethyl-4-chloroquinoline-3-carboxylate (V), which is finally cyclized with 4-chlorophenylhydrazine (VIII) by heating at 105 C in xylene. (VIII) is prepared in the usual way starting from 4-chloroaniline (IX) by diazotation with NaNO2-HCl to 4-chlorophenyldiazonium chloride (X), and reduction with SnCl2-HCl.

参考文献 中间体
合成目标
【1】 Yokoyama, N.; US 4312870 .
【2】 Yokoyama, N.; EP 0022078 .
【3】 Ritter, B.; Yokoyama, N.; Neubert, A.D.; 2-Arylpyrazolo[4,3-c]quinolin-3-ones: A partial novel agonist and antagonist of benzodiazepines. J Med Chem 1982, 25, 4, 337-339.
【4】 Castaner, J.; Blancafort, P.; Grau, M.; Serradell, M.N.; CGS-8216 and CGS-9896. Drugs Fut 1983, 8, 2, 99.
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) 12294 Aniline; Phenylamine 62-53-3 C6H7N 详情 详情
(II) 14088 Diethyl ethoxymethylenemalonate; Diethyl 2-(ethoxymethylene)malonate 87-13-8 C10H16O5 详情 详情
(III) 35953 diethyl 2-(anilinomethylene)malonate C14H17NO4 详情 详情
(IV) 35954 ethyl 4-hydroxy-3-quinolinecarboxylate C12H11NO3 详情 详情
(V) 35955 ethyl 4-chloro-3-quinolinecarboxylate C12H10ClNO2 详情 详情
(VIII) 33345 1-(4-chlorophenyl)hydrazine; 4-Chlorophenylhydrazine 1073-70-7 C6H7ClN2 详情 详情
(IX) 12034 4-Chlorophenylamine; 4-Chloroaniline; p-Chloroaniline 106-47-8 C6H6ClN 详情 详情
(X) 10197 4-Chlorobenzenediazonium chloride C6H4Cl2N2 详情 详情

合成路线4

该中间体在本合成路线中的序号：(I)

The reaction of p-chloroaniline (I) with ethyl 4-oxopiperidine-1-carboxylate (II) by means of tosyl chloride in refluxing toluene gives ethyl 4-(p-chlorophenylimino)piperidine-1-carboxylate (III), which is reduced with NaBH4 in refluxing methanol to afford ethyl 4-(p-chloroanilino)piperidine-1-carboxylate (IV). The acylation of (IV) with phenylacetyl chloride (A) in refluxing benzene yields ethyl 4-[N-(p-chlorophenyl)-N-(phenylacetyl)amino]piperidine-1-carboxylate (V), which is decarboxylated with hot aqueous HBr giving N-(p-chlorophenyl)-N-(piperidin-4-yl)phenylacetamide hydrochloride (VI). Finally, this compound is alkylated with 2-bromopropane (B) and Na2CO3 in refluxing butanol.

参考文献 中间体
合成目标
【1】 Hermans, H.K.; Sanczuk, S.; N-aryl-N-(1-L-4-piperidinyl)-arylacetamides. BE 0846473; US 4151286; US 4157393; ZA 7605684 .
【2】 Castaner, J.; Weetman, D.F.; Lorcainide hydrochloride. Drugs Fut 1978, 3, 7, 518.
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) 25890 2-phenylacetyl chloride；Phenylacetyl chloride;Phenacetyl chloride;Benzeneacetyl chloride 103-80-0 C8H7ClO 详情 详情
(B) 32658 2-bromopropane 75-26-3 C3H7Br 详情 详情
(I) 12034 4-Chlorophenylamine; 4-Chloroaniline; p-Chloroaniline 106-47-8 C6H6ClN 详情 详情
(II) 13486 Ethyl 4-oxo-1-piperidinecarboxylate; N-Carbethoxy-4-piperidone 29976-53-2 C8H13NO3 详情 详情
(III) 33565 ethyl 4-[(4-chlorophenyl)imino]-1-piperidinecarboxylate C14H17ClN2O2 详情 详情
(IV) 33566 ethyl 4-(4-chloroanilino)-1-piperidinecarboxylate C14H19ClN2O2 详情 详情
(V) 33567 ethyl 4-[4-chloro(2-phenylacetyl)anilino]-1-piperidinecarboxylate C22H25ClN2O3 详情 详情
(VI) 33568 N-(4-chlorophenyl)-2-phenyl-N-(4-piperidinyl)acetamide C19H21ClN2O 详情 详情

合成路线5

该中间体在本合成路线中的序号：(X)

N-trifluoroethyl derivative (III) can also be obtained by alkylation of (X) with (II) in refluxing xylene giving 4-chloro-N-(2,2,2-trifluoroethyl)aniline (XV), followed by a Friedel-Crafts reaction with benzoyl chloride by means of AlCl3.

参考文献 中间体
合成目标
【1】 Topliss, J.G.; 1-Polyhalogenoalkyl-2-oxo-1,3-dihydro-2H-14-benzodiazepines. US 3429874 .
【2】 Topliss, J.G.; 2-Polyfluoroweralkyl benzophenones. US 3641147 .
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(II) 33474 2,2,2-Trifluoroethyl trichloromethanesulfonate; 2,2,2-Trifluoroethyl trichloromethylsulfonate 23199-56-6 C3H2Cl3F3O3S 详情 详情
(III) 33848 [5-chloro-2-[(2,2,2-trifluoroethyl)amino]phenyl](phenyl)methanone C15H11ClF3NO 详情 详情
(X) 12034 4-Chlorophenylamine; 4-Chloroaniline; p-Chloroaniline 106-47-8 C6H6ClN 详情 详情
(XV) 33475 N-(4-chlorophenyl)-N-(2,2,2-trifluoroethyl)amine; 4-chloro-N-(2,2,2-trifluoroethyl)aniline C8H7ClF3N 详情 详情

合成路线6

该中间体在本合成路线中的序号：(X)

The starting benzophenone (I) can also be obtained in several different ways: a) By a Friedel-Crafts reaction of p-chloroaniline (X) and benzoyl chloride (D). b) By reaction of 5-chloroanthranilic acid (XI) with acetic anhydride to the bicyclic compound (XII), which is then submitted to a Grignard reaction with phenylmagnesium bromide (E). c) By oxidation of 2,3-diphenyl-5-chloroindole (XIII) with CrO3 to the N-benzoylbenzophenone (XIV), followed by debenzoylation with NaOH.

参考文献 中间体
合成目标
【1】 Topliss, J.G.; 1-Polyhalogenoalkyl-2-oxo-1,3-dihydro-2H-14-benzodiazepines. US 3429874 .
【2】 Topliss, J.G.; 2-Polyfluoroweralkyl benzophenones. US 3641147 .
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(D) 10463 Benzoyl chloride 98-88-4 C7H5ClO 详情 详情
(E) 17616 bromo(phenyl)magnesium; Phenyl Magnesium Bromide 100-58-3 C6H5BrMg 详情 详情
(I) 10279 (2-Amino-5-chlorophenyl)(phenyl)methanone; 2-Amino-5-chlorobenzophenone 719-59-5 C13H10ClNO 详情 详情
(X) 12034 4-Chlorophenylamine; 4-Chloroaniline; p-Chloroaniline 106-47-8 C6H6ClN 详情 详情
(XI) 10285 2-Amino-5-chlorobenzoic acid 635-21-2 C7H6ClNO2 详情 详情
(XII) 33853 6-chloro-2-methyl-4H-3,1-benzoxazin-4-one C9H6ClNO2 详情 详情
(XIII) 33854 5-chloro-2,3-diphenyl-1H-indole C20H14ClN 详情 详情
(XIV) 33855 N-(2-benzoyl-4-chlorophenyl)benzamide C20H14ClNO2 详情 详情

合成路线7

该中间体在本合成路线中的序号：(XIII)

The condensation of p-chlorophenyldiazonium chloride (from p-chloroaniline (XIII) and NaNO2-HCl) and ethyl o-fluorobenzylacetoacetate (XIV) in methanol-water gives ethyl alpha-(o-fluorobenzyl)-alpha-(p-chlorophenylazo) acetoacetate (XV), which is cyclized to indole (XII) by means of H2SO4 in refluxing isopropanol.

参考文献 中间体
合成目标
【1】 Yamamoto, H.; et al.; ZA 6806061 .
【2】 Yamamoto, H.; et al. (Sumitomo Chemical Co., Ltd.); Process for producing benzodiazepine derivatives. US 3632574 .
【3】 Blancafort, P.; Serradell, M.N.; Castaner, J.; KB-509. Drugs Fut 1979, 4, 10, 720.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(XII) 33347 ethyl 5-chloro-3-(2-fluorophenyl)-1H-indole-2-carboxylate C17H13ClFNO2 详情 详情
(XIII) 12034 4-Chlorophenylamine; 4-Chloroaniline; p-Chloroaniline 106-47-8 C6H6ClN 详情 详情
(XIV) 33348 ethyl 2-(2-fluorobenzyl)-3-oxobutanoate C13H15FO3 详情 详情
(XV) 33349 ethyl 2-[(Z)-2-(4-chlorophenyl)diazenyl]-2-(2-fluorobenzyl)-3-oxobutanoate C19H18ClFN2O3 详情 详情

合成路线8

该中间体在本合成路线中的序号：(III)

1) 5-Indansulfonamide (I) is converted to ethyl N-(5-indansulfonyl)carbamate (II) with ethyl chloroformate and potassium carbonate in refluxing 2-butanone, which is then reacted with 4-chloroaniline (III) in toluene at reflux to provide sulofenur. 2) Alternatively, (I) can be converted to its anion with NaOH in aqueous acetone, then reacted with 4-chlorophenylisocyanate (IV) to give sulofenur directly.

参考文献 中间体
合成目标
【1】 Grindey, G.B.; Indentification of diarylsulfonylureas as novel anticancer drugs. Proc Amer Assoc Cancer Res 1988, 29, 553-6.
【2】 Grossman, C.S.; Kramer, K.E.; Crowell, T.A.; Grindey, G.B.; Rieder, B.J.; Rinzel, S.M.; Harper, R.W.; Howbert, J.J.; Tao, E.V.; Aikins, J.; Shaw, W.N.; Poore, G.A.; Todd, G.C.; Novel agents effective against solid tumors: The diarylsulfonylureas. Synthesis, activities and analysis of quantitative structure-activity relationships. J Med Chem 1990, 33, 9, 2393-407.
【3】 Howbert, J.J.; Sulofenur. Drugs Fut 1991, 16, 6, 517.
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) 12032 5-Indanesulfonamide 35203-93-1 C9H11NO2S 详情 详情
(II) 12033 ethyl N-(2,3-dihydro-1H-inden-5-ylsulfonyl)carbamate C12H15NO4S 详情 详情
(III) 12034 4-Chlorophenylamine; 4-Chloroaniline; p-Chloroaniline 106-47-8 C6H6ClN 详情 详情
(IV) 12035 4-chlorophenyl isocyanate; 1-Chloro-4-isocyanatobenzene; p-Chlorophenyl isocyanate 104-12-1 C7H4ClNO 详情 详情

合成路线9

该中间体在本合成路线中的序号：(B)

Two different routes have been described for the preparation of title compound: 1) 3-Methyl-5-aminoisothiazole-4-carboxylic acid (I) is reacted with benzoyl chloride in acetone solution and in the presence of pyridine to yield the benzamide (II), which by reaction with SOCl2 is converted to the lactam (III). The reaction of lactam (III) with p-chloroaniline in anhydrous ethanol gives the p-chlorophenylamide (vratizolin). 2) The reaction of 3-methyl-5-benzoylamino-4-isothiazolecarboxylic acid (II) with chloroformic ethyl ester gives the mixed anhydride, which, when heated with p-chloroanitine in anhydrous ethanol forms title compound. Vratizolin is also a product of the reaction of the acid (II) with p-chloroaniline in the presence of dicyclohexylcarbodiimide.

参考文献 中间体
合成目标
【1】 Kolwas, J.; ITCI. Drugs Fut 1981, 6, 8, 475.
【2】 Machon, Z.; et al.; New isothiazole derivatives. I. Relations between chemical structure and biological activities. Arch Immunol Ther Exp 1973, 21, 6, 883-889.
【3】 Machon, Z.; p-Chlorophenylamide of 3-methyl-5-benzoyl-aminoiso. Arch Immunol Ther Exp 1983, 31, 579.
【4】 Machon, Z.; Synthesis and properties of 3-methyl-5-benzoylaminoiothiazole-4-carboxilic acid derivatives. Diss Pharm Pharmacol 1969, 21, 4, 325.
【5】 Machon, Z.; Vratizolin. Drugs Fut 1988, 13, 5, 426.
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) 10473 (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetoxy)-1,15-dihydroxy-10,14,17,17-tetramethyl-11-oxo-9-[(triethylsilyl)oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate C37H52O11Si 详情 详情
(B) 12034 4-Chlorophenylamine; 4-Chloroaniline; p-Chloroaniline 106-47-8 C6H6ClN 详情 详情
(I) 22621 5-amino-3-methyl-4-isothiazolecarboxylic acid C5H6N2O2S 详情 详情
(II) 22622 5-(benzoylamino)-3-methyl-4-isothiazolecarboxylic acid C12H10N2O3S 详情 详情
(III) 22623 7-benzoyl-4-methyl-2-thia-3,7-diazabicyclo[3.2.0]hept-3-en-6-one C12H10N2O2S 详情 详情

合成路线10

该中间体在本合成路线中的序号：(I)

Efavirenz has been obtained by two related ways: 1) The acylation of 4-chloroaniline (I) with pivaloyl chloride (II) by means of Na2CO3 in toluene gives the expected anilide (III), which is acylated with ethyl trifluoroacetate by means of butyllithium in THF yielding, after hydrolysis with HCl, 2'-amino-5'-chloro-2,2,2-trifluoroacetophenone (IV). The benzylation of (IV) with 4-methoxybenzyl chloride (V) in basic alumina affords the protected acetophenone (VI), which is regioselectively condensed with cyclopropylacetylene (VII) [obtained by cyclization of 5-chloro-1-pentyne (VIII) by means of butyllithium in cyclohexane] by means of butyllithium in THF in the presence of (1R,2S)-1-phenyl-2-(1-pyrrolidinyl)-1-propanol (IX) giving the (S)-isomer of the tertiary alcohol (X) exclusively. The cyclization of (X) with phosgene and triethylamine or K2CO3 in toluene/THF yields the benzoxazinone (XI), which is finally deprotected with ceric ammonium nitrate in acetonitrile/water. 2) The condensation of 2'-amino-5'-chloro-2,2,2-trifluoroacetophenone (IV) with cyclopropylacetylene (VIII) by means of butyllithium or ethylmagnesium bromide in THF gives (?-2-(2-amino-5-chlorophenyl)-4-cyclopropyl-1,1,1-trifluoro-3-butyn-2-ol (XII). The cyclization of (XII) with carbonyldiimidazole (XIII) in hot THF yields the racemic benzoxazinone (XIV). Compound (XIV) is submitted to optical resolution by condensation with (S)-(-)-camphanoyl chloride by means of dimethylaminopyridine (DMAP) in dichloromethane to give the acyl derivative (XVI) as a diastereomeric mixture that is resolved by crystallization and finally decomposed with HCl in ethanol or butanol.

参考文献 中间体
合成目标
【1】 Choudhury, A.; Moore, J.R.; Pierce, M.E.; Fortunak, J.M.; Valvis, I.; Confalone, P.N.; In situ recycling of chiral ligand and surplus nucleophile for a noncatalytic reaction: Amplification of process throughput in the asymmetric addition step of efavirenz (DMP 266). Org Process Res Dev 2003, 7, 3, 324.
【2】 Britcher, S.F.; Tran, L.O.; Young, S.D.; L-743,726 (DMP-266): A novel, highly potent nonnucleoside inhibitor of the human immunodeficiency virus type 1 reverse transcriptase. Antimicrob Agents Chemother 1995, 39, 12, 2602-5.
【3】 Corley, E.G.; Thompson, A.S.; Huntington, M.F.; Grabowski, E.J.J.; Use of an ephedrine alkoxide to mediate enantioselective addition of an acetylide to a prochiral ketone: Asymmetric synthesis of the reverse transcriptase inhibitor L-743,726. Tetrahedron Lett 1995, 36, 49, 8937-40.
【4】 Graul, A.; Rabasseda, X.; Castañer, J.; Efavirenz. Drugs Fut 1998, 23, 2, 133.
【5】 Young, S.D.; Britcher, S.F.; Payne, L.S.; Tran, L.O.; Lumma, W.C. Jr. (Merck & Co., Inc.); Benzoxazinones as inhibitors of HIV reverse transcriptase. WO 9520389 .
【6】 Young, S.D.; Tran, L.O.; Britcher, S.F.; Lumma, W.C. Jr.; Payne, L.S. (Merck & Co., Inc.); Benzoxazinones as inhibitors of HIV reverse transcriptase. EP 0582455; JP 1994184124; WO 9403440 .
【7】 Thompson, A.S.; Corley, E.G.; Huntington, M. (Merck & Co., Inc.); Improved synthesis of cyclopropylacetylene. JP 1998512880; WO 9622955 .
【8】 Thompson, A.S.; Corley, E.G.; Grabowski, E.J.J.; Yasuda, N. (Merck & Co., Inc.); Asymmetric synthesis of (-)-6-chloro-4-cyclopropylethynyl-4-trifluoromethyl-1,4-dihydro-2H-3,1 -benzoxazin-2-one. WO 9637457 .
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) 12034 4-Chlorophenylamine; 4-Chloroaniline; p-Chloroaniline 106-47-8 C6H6ClN 详情 详情
(II) 13597 2,2-Dimethylpropanoyl chloride; Pivaloyl chloride 3282-30-2 C5H9ClO 详情 详情
(III) 16571 4'-Chloro-2,2-dimethylpropionanilide; N-(4-Chlorophenyl)-2,2-dimethylpropanamide 65854-91-3 C11H14ClNO 详情 详情
(IV) 16572 1-(2-amino-5-chlorophenyl)-2,2,2-trifluoro-1-ethanone C8H5ClF3NO 详情 详情
(V) 11910 4-Methoxybenzyl chloride; 1-(Chloromethyl)-4-methoxybenzene; alpha-Chloro-4-methoxytoluene; 4-(Chloromethyl)phenyl methyl ether 824-94-2 C8H9ClO 详情 详情
(VI) 16574 1-[5-chloro-2-[(4-methoxybenzyl)amino]phenyl]-2,2,2-trifluoro-1-ethanone C16H13ClF3NO2 详情 详情
(VII) 16575 1-ethynylcyclopropane; cyclopropyl acetylene 6746-94-7 C5H6 详情 详情
(VIII) 16576 5-chloro-1-pentyne 14267-92-6 C5H7Cl 详情 详情
(IX) 16577 (1R,2S)-1-phenyl-2-(1-pyrrolidinyl)-1-propanol C13H19NO 详情 详情
(X) 16578 (2S)-2-[5-chloro-2-[(4-methoxybenzyl)amino]phenyl]-4-cyclopropyl-1,1,1-trifluoro-3-butyn-2-ol C21H19ClF3NO2 详情 详情
(XI) 16579 (4S)-6-chloro-4-(2-cyclopropylethynyl)-1-(4-methoxybenzyl)-4-(trifluoromethyl)-1,4-dihydro-2H-3,1-benzoxazin-2-one C22H17ClF3NO3 详情 详情
(XII) 16580 2-(2-amino-5-chlorophenyl)-4-cyclopropyl-1,1,1-trifluoro-3-butyn-2-ol 168834-43-3 C13H11ClF3NO 详情 详情
(XIII) 11353 1,1'-Carbonyldiimidazole; Di(1H-imidazol-1-yl)methanone; N,N-Carbonyldiimidazole; 1,1'-Carbonylbis(1H-imidazole) 530-62-1 C7H6N4O 详情 详情
(XIV) 16582 6-chloro-4-(2-cyclopropylethynyl)-4-(trifluoromethyl)-1,4-dihydro-2H-3,1-benzoxazin-2-one C14H9ClF3NO2 详情 详情
(XV) 16583 (1S,4R)-4,7,7-trimethyl-3-oxo-2-oxabicyclo[2.2.1]heptane-1-carbonyl chloride; (-)-Camphanic chloride 39637-74-6 C10H13ClO3 详情 详情
(XVI) 16584 6-chloro-4-(2-cyclopropylethynyl)-4-(trifluoromethyl)-1-[[(4R)-4,7,7-trimethyl-3-oxo-2-oxabicyclo[2.2.1]hept-1-yl]carbonyl]-1,4-dihydro-2H-3,1-benzoxazin-2-one C24H21ClF3NO5 详情 详情

合成路线11

该中间体在本合成路线中的序号：(I)

The synthesis of AWD 131-138 is obtained as illustrated in Scheme 25002101a: The alkylation of 4-chloroaniline (I) with chloroacetic acid methyl ester in ethanol gives N-(4-chlorophenyl)glycine methyl ester (II), which is added to cyanate by means of hydrochloric acid in glacial acetic acid to yield 3-(4-chlorophenyl)hydantoic acid methyl ester (III). The cyclization in hydrochloric acid yields 1-(4-chlorophenyl)hydantoin (IV), which is finally condensed with morpholine.

参考文献 中间体
合成目标
【1】 Tober, C.; Unverferth, K.; Stark, B.; Rostock, A.; Dost, R.; Kronbach, T.; Schupke, H.; Bartsch, R.; Egerland, U.; Lankau, H-J.; Rundfeldt, C.; AWD-131-138. Drugs Fut 1998, 23, 3, 253.
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) 12034 4-Chlorophenylamine; 4-Chloroaniline; p-Chloroaniline 106-47-8 C6H6ClN 详情 详情
(II) 17280 methyl 2-(4-chloroanilino)acetate C9H10ClNO2 详情 详情
(III) 17281 methyl 2-[(aminocarbonyl)-4-chloroanilino]acetate C10H11ClN2O3 详情 详情
(IV) 17282 1-(4-chlorophenyl)-1H-imidazole-2,4(3H,5H)-dione C9H7ClN2O2 详情 详情

合成路线12

该中间体在本合成路线中的序号：(III)

5) The reaction of L-ornithine (III) with benzaldehyde by means of LiOH gives Ndelta-benzylidene-L-ornitine (XIII), which is treated first with benzyl chloroformate and NaOH and hydrolyzed with HCl to afford Nalpha-(benzyloxycarbonyl)-L-ornithine (XIV). The condensation of (XIV) with N,S-dimethylisothiouronium iodide (II) by means of NaOH gives Nalpha-(benzyloxycarbonyl)-Nomega-methyl-L-arginine (XV), which is finally deprotected by hydrogenation with H2 over Pd/C.

参考文献 中间体
合成目标
【1】 Sala, A.; Ferrario, F.; Trupiano, F.; Levi, S.; Multigram synthesis of NG-methyl-(L-)-arginine and its analytical characterization. Synth Commun 1991, 21, 99-105.
【2】 Wroblewski, T.; Castañer, J.; Prous, J.R.; 546C88. Drugs Fut 1998, 23, 2, 123.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(II) 17284 (methylamino)(methylsulfanyl)methaniminium iodide C3H9IN2S 详情 详情
(III) 12034 4-Chlorophenylamine; 4-Chloroaniline; p-Chloroaniline 106-47-8 C6H6ClN 详情 详情
(III) 17285 L-ornithine 70-26-8 C5H12N2O2 详情 详情
(XIII) 17291 (2S)-2-amino-5-[[(E)-benzylidene]amino]pentanoic acid C12H16N2O2 详情 详情
(XIV) 17292 (2S)-5-amino-2-[[(benzyloxy)carbonyl]amino]pentanoic acid C13H18N2O4 详情 详情
(XV) 17293 (2S)-2-[[(benzyloxy)carbonyl]amino]-5-[[imino(methylamino)methyl]amino]pentanoic acid C15H22N4O4 详情 详情

合成路线13

该中间体在本合成路线中的序号：(V)

Condensation of phthalic anhydride (I) with 4-methylpyridine (II) and heating with NH2-NH2 hydrate yields phthalazine (III) which is converted into chloro derivative (IV) by directly heating in presence of POCl3 or alternatively by heating a solution of (IV) in CH3CN with HCl/dioxane and POCl3. Phthalazine (III) is added to a melt formed by 4-chloroaniline (V), P2O5 and Et3N.HCl to afford the desired product. Alternatively the final product is obtained by heating (V) with (IV) in EtOH or 1-butanol.

参考文献 中间体
合成目标
【1】 DE 1061788; GB 871753 .
【2】 Altmann, K.-H.; Mett, H.; Wood, J.; Stover, D.R.; Frei, J.; Bold, G.; Traxler, P. (Novartis AG); Phthalazines with angiogenesis inhibiting activity. EP 0970070; WO 9835958 .
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) 11900 2-Benzofuran-1,3-dione;1,2-Benzenedicarboxylic Anhydride;1,2-BENZENE DICARBOXYLIC ACID ANHYDRIDE;1,2-BENZENEDICARBONIC ACID, ANHYDRIDE;1,3-DIOXOPHTHALAN;1,3-ISOBENZOFURANDIONE;o-phthalic anhydride; Phthalic anhydride 85-44-9 C8H4O3 详情 详情
(II) 31150 4-methylpyridine 108-89-4 C6H7N 详情 详情
(III) 41366 4-(4-pyridinylmethyl)-1,2-dihydro-1-phthalazinol C14H13N3O 详情 详情
(IV) 41367 1-chloro-4-(4-pyridinylmethyl)phthalazine C14H10ClN3 详情 详情
(V) 12034 4-Chlorophenylamine; 4-Chloroaniline; p-Chloroaniline 106-47-8 C6H6ClN 详情 详情

合成路线14

该中间体在本合成路线中的序号：(VI)

The reaction of phthalide (I) with pyridine-4-carbaldehyde (II) by means of NaOMe in methanol gives the nonisolated intermediate (III), which rearranges in the reaction medium to yield indenone (IV). The reaction of (IV) with hydrazine affords the phthalazinone (V), which is finally condensed with 4-chloroaniline (VI) by means of P2O5 and TEA at 170 C to provide the target phthalazine.

参考文献 中间体
合成目标
【1】 Manly, D.G.; Tilford, C.H.; Richardson, A.; Stock, A.M.; Amstutz, E.D.; A Study of the chemistry of pyrophthalone and related compounds. J Org Chem 1958, 23, 373-80.
【2】 Letourneux, Y.; Floc'h, R.; Le Baut, G.; Ploquin, J.; Sparfel, L.; beta-Dicéto énamines hétérocycliques: 1. Indanediones-1,3-disubstitutées en 2 par un hétérocycle azoté. J Heterocycl Chem 1980, 17, 961-73.
【3】 Andersen, L.; Pedersen, E.B.; Synthesis of 4-arylamino-1H-pyrazolo[3,4-d]pyrimidines. Acta Chem Scand Ser b 1988, B42, 492-3.
【4】 Manley, P.W.; Martiny-Baron, G.; Brüggen, J.; Mestan, J.; Meyer T.; Wood, J.M.; Ferrari, S.; Hofmann, F.; Bold, G.; Frei, J.; Furet, P.; Cozens, R.M.; CGP 79787D (PTK787/ZK222584), CGP 84738, NVP-AAC789, NVP-AAD777 and related 1-anilino-(4-pyridylmethyl)phthalazines as inhibitors of VEGF- and bFGF-induced angiogenesis. Drugs Fut 2002, 27, 1, 43.
【5】 Frei, J.; Bold, G.; Altmann, K.-H.; et al.; New anilinophthalazines as potent and orally well absorbed inhibitors of the VEGF receptor tyrosine kinases useful as antagonists of tumor-driven angiogenesis. J Med Chem 2000, 43, 12, 2310.
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) 12576 2-Benzofuran-1(3H)-one; Phthalide; Benzo[b]furan-1(3H)-one; 1(3H)-Isobenzofuranoneisobenzofuran-1-one 87-41-2 C8H6O2 详情 详情
(II) 17203 4-Pyridinecarboxaldehyde; isonicotinaldehyde 872-85-5 C6H5NO 详情 详情
(III) 49917 3-[(Z)-4-pyridinylmethylidene]-2-benzofuran-1-one C14H9NO2 详情 详情
(IV) 49918 3-hydroxy-2-(4-pyridinyl)-1H-inden-1-one C14H9NO2 详情 详情
(V) 49919 4-(4-pyridinylmethyl)-1(2H)-phthalazinone C14H11N3O 详情 详情
(VI) 12034 4-Chlorophenylamine; 4-Chloroaniline; p-Chloroaniline 106-47-8 C6H6ClN 详情 详情

合成路线15

该中间体在本合成路线中的序号：(IV)

Friedel-Crafts acylation of chlorobenzene (I) with levulinic acid chloride (II) afforded diketone (III), which was converted to pyrrole (V) by condensation with 4-chloroaniline (IV) in the presence of a catalytic amount of HBr. Mannich reaction of (V) with formaldehyde and N-methylpiperazine (VI) then provided the target aminomethyl pyrrole.

参考文献 中间体
合成目标
【1】 Retico, A.; Cerreto, F.; Scalzo, M.; Villa, A.; Studies on anti-Candida agents with a pyrrole moiety. Synthesis and microbiological activity of some 3-aminomethyl-1,5-diaryl-2-methyl-pyrrole derivatives. Eur J Med Chem 1992, 27, 7, 701.
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) 10190 1-Chlorobenzene 108-90-7 C6H5Cl 详情 详情
(II) 28526 4-oxopentanoyl chloride C5H7ClO2 详情 详情
(III) 28527 1-(4-chlorophenyl)-1,4-pentanedione C11H11ClO2 详情 详情
(IV) 12034 4-Chlorophenylamine; 4-Chloroaniline; p-Chloroaniline 106-47-8 C6H6ClN 详情 详情
(V) 28528 1,2-bis(4-chlorophenyl)-5-methyl-1H-pyrrole C17H13Cl2N 详情 详情
(VI) 10061 1-Methylpiperazine; 1-Methyl piperazine; N-Methylpiperazine 109-01-3 C5H12N2 详情 详情

合成路线16

该中间体在本合成路线中的序号：(I)

Reaction of 4-chloroaniline (I) with gamma-butyrolactone (II) in a refluxing solution of HCl afforded pyrrolidinone (III). Subsequent carboxylation of (III) with diethyl carbonate in the presence of NaH gave ketoester (IV), which was reduced to alcohol (V) using calcium borohydride in MeOH. Further treatment of (V) with methanesulfonyl chloride and Et3N provided the corresponding mesylate (VI). Methoxyethylpiperazine (IX) was prepared by alkylation of formylpiperazine (VII) with 2-methoxyethyl bromide, followed by acid deprotection of the alkylated formylpiperazine (VIII). Then, condensation of mesylate (VI) with piperazine (IX) provided racemic (X). Finally, resolution with D-tartaric acid in EtOH yielded the target (R)-isomer.

参考文献 中间体
合成目标
【1】 Mita, N.; Nagase, H.; Iizuka, H.; Oguchi, T.; Sakai, K.; Horikomi, K.; Miwa, T.; Takahashi, S. (Mitsui Chemicals, Inc.); Pyrrolidinone derivs. and their use as antipsychotic medicaments. EP 0839805; JP 1998182602 .
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) 12034 4-Chlorophenylamine; 4-Chloroaniline; p-Chloroaniline 106-47-8 C6H6ClN 详情 详情
(II) 20576 dihydro-2(3H)-furanone 96-48-0 C4H6O2 详情 详情
(III) 27732 1-(4-chlorophenyl)-2-pyrrolidinone 7661-33-8 C10H10ClNO 详情 详情
(IV) 27733 ethyl 1-(4-chlorophenyl)-2-oxo-3-pyrrolidinecarboxylate C13H14ClNO3 详情 详情
(V) 27734 1-(4-chlorophenyl)-3-(hydroxymethyl)-2-pyrrolidinone C11H12ClNO2 详情 详情
(VI) 27735 [1-(4-chlorophenyl)-2-oxo-3-pyrrolidinyl]methyl methanesulfonate C12H14ClNO4S 详情 详情
(VII) 23801 1-piperazinecarbaldehyde; N-Formylpiperazine 7755-92-2 C5H10N2O 详情 详情
(VIII) 27736 4-(2-methoxyethyl)-1-piperazinecarbaldehyde C8H16N2O2 详情 详情
(IX) 27737 1-(2-methoxyethyl)piperazine C7H16N2O 详情 详情
(X) 27738 1-(4-chlorophenyl)-3-[[4-(2-methoxyethyl)-1-piperazinyl]methyl]-2-pyrrolidinone C18H26ClN3O2 详情 详情

合成路线17

该中间体在本合成路线中的序号：(I)

Synthesis of Intermediate (VII): Acylation of p-chloroaniline (I) with dimethylmalonic acid (A) and SOCl2 gives (II), which is then cyclized to quinolinedione (III) by means of P2O5 in CH3SO3H. Reduction of the carbonyl groups of (III) with LiAlH4 in THF/Et2O in presence of AlCl3 provides tetrahydroquinoline (IV), which is further sulfonated with pyridine/SO3, yielding derivative (V). Removal of the chloro substituent of (V) by hydrogenation in basic conditions (in the presence of either NaHCO3/H2O or Et3N in MeOH) affords sulfonic acid (VI), which is converted to the sulfonyl chloride (VII) by means of ultrasound in acetonitrile or 1,3-dimethylimidazolidin-2-one (DMID) followed by treatment with POCl3 in pyridine. This conversion can also be achieved by treatment with PPh3 in dichloromethane and sulfuryl chloride. Alternatively, (V) can be converted into (VII) by a first sulfonation to yield (VIII) followed by removal of the chloro substituent in the same conditions described above. Intermediate (VI) can also be obtained as follows: Bromination of quinolinone (IX) with Br2 in CHCl3 yields derivative (X), which is then reduced with LiAlH4/AlCl3 in THF/Et2O to give tetrahydroquinoline (XI). (XI) is then converted into (XII) by sulfonation with DMF/sulfur trioxide complex. Finally, hydrogenation of (XII) over Pd/C in the presence of NaHCO3 allows removal of the bromo substituent, providing (VI).

参考文献 中间体
合成目标
【1】 Donovan, V.; Brundish, D.; Bull, A.; et al.; Design and synthesis of thrombin inhibitors: Analogues of MD-805 with reduced stereogenicity and improved potency. J Med Chem 1999, 42, 22, 4584.
【2】 Hoyle, W.; Howarth, G.A.; Brundish, D.E.; Kane, P.D.; Walker, C.V.; Hayler, J.; Fullerton, J.D.; Smith, G.P.; Wathey, W.B.; Le Grand, D.M.; Allen, M.C.; Herold, P. (Novartis AG); Trypsin and thrombin inhibitors. EP 0815103; JP 1999502219; WO 9629327 .
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) 42999 2,2-dimethylmalonic acid 595-46-0 C5H8O4 详情 详情
(I) 12034 4-Chlorophenylamine; 4-Chloroaniline; p-Chloroaniline 106-47-8 C6H6ClN 详情 详情
(II) 43000 3-(4-chloroanilino)-2,2-dimethyl-3-oxopropionic acid C11H12ClNO3 详情 详情
(III) 43001 6-chloro-3,3-dimethyl-2,4(1H,3H)-quinolinedione C11H10ClNO2 详情 详情
(IV) 43002 3,3,6-trimethyl-1,2,3,4-tetrahydroquinoline C12H17N 详情 详情
(V) 43003 6-chloro-3,3-dimethyl-1,2,3,4-tetrahydro-8-quinolinesulfonic acid C11H14ClNO3S 详情 详情
(VI) 43004 3,3-dimethyl-1,2,3,4-tetrahydro-8-quinolinesulfonic acid C11H15NO3S 详情 详情
(VII) 43005 3,3-dimethyl-1,2,3,4-tetrahydro-8-quinolinesulfonyl chloride C11H14ClNO2S 详情 详情
(VIII) 43006 6-chloro-3,3-dimethyl-1,2,3,4-tetrahydro-8-quinolinesulfonyl chloride C11H13Cl2NO2S 详情 详情
(IX) 43007 3,3-dimethyl-3,4-dihydro-2(1H)-quinolinone C11H13NO 详情 详情
(X) 43008 6-bromo-3,3-dimethyl-3,4-dihydro-2(1H)-quinolinone C11H12BrNO 详情 详情
(XI) 43009 6-bromo-3,3-dimethyl-1,2,3,4-tetrahydroquinoline C11H14BrN 详情 详情
(XII) 43010 6-bromo-3,3-dimethyl-1,2,3,4-tetrahydro-8-quinolinesulfonic acid C11H14BrNO3S 详情 详情

合成路线18

该中间体在本合成路线中的序号：(I)

The reaction of 4-chloroaniline (I) with di(2-pyridyl)thione (DPT) gives the corresponding isothiocyanate (II), which is condensed with cyanamide (III) and 2-bromo-1-(3-benzyloxyphenyl)ethanone (IV) by means of NaOMe to yield the adduct (V). This compound, without isolation, cyclizes to the target thiazole.

参考文献 中间体
合成目标
【1】 Sorensen, A.R.; Engelhardt, S.; Kurtzhals, P.; Urso, B.; Bowler, A.N.; 2,4-Diaminothiazoles: A novel class of glycogen synthase kinase-3 (GSK-3) inhibitors. 11th RSC-SCI Med Chem Symp (Sept 9 2001, Cambridge) 2001, Abst P20.
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) 12034 4-Chlorophenylamine; 4-Chloroaniline; p-Chloroaniline 106-47-8 C6H6ClN 详情 详情
(II) 22146 1-isothiocyanatobenzene; phenyl isothiocyanate 103-72-0 C7H5NS 详情 详情
(III) 19648 Cyanamide 420-04-2 CH2N2 详情 详情
(IV) 53541 1-[3-(benzyloxy)phenyl]-2-bromo-1-ethanone n/a C15H13BrO2 详情 详情
(V) 53545 (Z)-3-({2-[3-(benzyloxy)phenyl]-2-oxoethyl}sulfanyl)-3-(4-chloroanilino)-2-propenenitrile n/a C24H19ClN2O2S 详情 详情

合成路线19

该中间体在本合成路线中的序号：(III)

The target piperazine-1-carboxamide has been obtained by several different methods: 1.- The condensation of 6,7-dimethoxy-4-(1-piperazinyl)quinazoline (I) with 4-chlorophenyl isocyanate (II) in DMF gives the target compound. 2.- The condensation of 6,7-dimethoxy-4-(1-piperazinyl)quinazoline (I) with 4-chlorophenylamine (III) by means of CDI or triphosgene also gives the target piperazine-1-carboxamide. 3.- The reaction of 4-chlorophenylamine (III) with 4-nitrophenyl chloroformate (IV) by means of TEA gives the carbamate (V), which is finally condensed with the quinazoline (I) in hot NMP to yield the target piperazine-1-carboxamide.

参考文献 中间体
合成目标
【1】 Matsuno, K.; Ichimura, M.; Nakajima, T.; Tahara, K.; Fujiwara, S.; Kase, H.; Ushiki, J.; Giese, N.A.; Pandey, A.; Scarborough, R.M.; Lokker, N.A.; Yu, J.C.; Irie, J.; Tsukuda, E.; Ide, S.-i; Oda, S.; Nomoto, Y.; Potent and selective inhibitors of platelet-derived growth factor receptor phosphorylation. 1. Synthesis, structure-activity relationship, and biological effects of a new class of quinazoline derivatives. J Med Chem 2002, 45, 14, 3057.
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) 41610 6,7-dimethoxy-4-(1-piperazinyl)quinazoline; 6-methoxy-4-(1-piperazinyl)-7-quinazolinyl methyl ether C14H18N4O2 详情 详情
(II) 12035 4-chlorophenyl isocyanate; 1-Chloro-4-isocyanatobenzene; p-Chlorophenyl isocyanate 104-12-1 C7H4ClNO 详情 详情
(III) 12034 4-Chlorophenylamine; 4-Chloroaniline; p-Chloroaniline 106-47-8 C6H6ClN 详情 详情
(IV) 16605 4-Nitrophenyl chloroformate; 1-[(Chlorocarbonyl)oxy]-4-nitrobenzene 7693-46-1 C7H4ClNO4 详情 详情
(V) 63171 4-nitrophenyl 4-chlorophenylcarbamate C13H9ClN2O4 详情 详情

合成路线20

该中间体在本合成路线中的序号：(VI)

Condensation of anthranilic acid (I) with 4-chloro-3-nitrobenzenesulfonyl chloride (II) in the presence of Na2CO3 affords sulfonamide (III). Electrophilic chlorination of (III) employing sulfuryl chloride in hot AcOH leads to (IV). After activation of acid (IV) as the corresponding acid chloride (V), coupling with 4-chloroaniline (VI) furnishes the target anthranilamide.

参考文献 中间体
合成目标
【1】 Allanson, N.M.; Thomas, M.G. (PanTherix Ltd.); Bactericidal benzamide derivs.. GB 2365426 .
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) 11661 2-Aminobenzoic acid;Anthranilic acid; o-Aminobenzoic acid 118-92-3 C7H7NO2 详情 详情
(II) 42319 tert-butyl (2S)-1-[(4-chloro-3-nitrophenyl)sulfonyl]-2-pyrrolidinecarboxylate C15H19ClN2O6S 详情 详情
(III) 64106 2-{[(4-chloro-3-nitrophenyl)sulfonyl]amino}benzoic acid C13H9ClN2O6S 详情 详情
(IV) 64107 5-chloro-2-{[(4-chloro-3-nitrophenyl)sulfonyl]amino}benzoic acid C13H8Cl2N2O6S 详情 详情
(V) 64108 5-chloro-2-{[(4-chloro-3-nitrophenyl)sulfonyl]amino}benzoyl chloride C13H7Cl3N2O5S 详情 详情
(VI) 12034 4-Chlorophenylamine; 4-Chloroaniline; p-Chloroaniline 106-47-8 C6H6ClN 详情 详情
Extended Information