|
【结 构 式】 
|
【分子编号】12591 【品名】Cyanoacetic Acid; 2-Cyanoacetic acid 【CA登记号】372-09-8 |
【 分 子 式 】C3H3NO2 【 分 子 量 】85.06236 【元素组成】C 42.36% H 3.55% N 16.47% O 37.62% |
合成路线1
该中间体在本合成路线中的序号：(VI)The reaction of N-propylurea (V) with cyanacetic acid (VI) in hot acetic anhydride gives N-propyl-N'-cyanacetylurea (VII), which is nitrosated with NaNO2 - HCl yielding the isonitroso derivative (VIII). The reduction and simultaneous formylation of (VIII) with Zn in formic acid affords the formylamino compound (IX), which is cyclized by treatment with NaOH to give 6-amino-5-formylamino-1-propylpyrimidine-2,4-dione (X). Finally, this compound is cyclized by treatment with refluxing formic acid. The cyclization of (VII) with NaOH in hot water gives 6-amino-1-propylpyrimidine-2,4-dione (XI), which is nitrosated with NaNO2 - HCl as usual yielding 6-amino-nitroso-1-propylpyrimidine-2,4-dione (XII). The reduction of (XII) with H2 over Pt in DMF affords 5,6-diamino-1-propylpyrimidine-2,4-dione (XIII), which is finally formylated with refluxing formic acid to (X). This compound can also be finally cyclized by treatment with NaOH in refluxing water.
| 【1】 Ohtsuka, Y.; Oxazolopyrimidines. VI. Formation of 3-substituted xanthines via 7-(6H)-iminooxazolopyrimidines. Bull Chem Soc Jpn 1973, 46, 2, 506-509. |
| 【2】 Kjellin, P.G.; Persson, C.G.A. (Draco Läkemedel AB); Method and pharmaceutical preparation for treating chronic obstructive airway disease and cardiac disease, and intermediates for the preparation of therapeutically active xanthine derivs.. EP 0011609 . |
| 【3】 Sneddon, J.M.; Castaner, J.; Blancafort, P.; Serradell, M.N.; Enprofylline. Drugs Fut 1982, 7, 9, 623. |
| 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) | 37133 | N-propylurea | C4H10N2O | 详情 | 详情 | |
| (VI) | 12591 | Cyanoacetic Acid; 2-Cyanoacetic acid | 372-09-8 | C3H3NO2 | 详情 | 详情 |
| (VII) | 37134 | N-(2-cyanoacetyl)-N'-propylurea | C7H11N3O2 | 详情 | 详情 | |
| (VIII) | 37135 | N-[2-cyano-2-(hydroxyimino)acetyl]-N'-propylurea | C7H10N4O3 | 详情 | 详情 | |
| (IX) | 37136 | N-[2-cyano-2-(formylamino)acetyl]-N'-propylurea | C8H12N4O3 | 详情 | 详情 | |
| (X) | 37137 | 6-amino-2,4-dioxo-1-propyl-1,2,3,4-tetrahydro-5-pyrimidinylformamide | C8H12N4O3 | 详情 | 详情 | |
| (XI) | 37138 | 6-amino-1-propyl-2,4(1H,3H)-pyrimidinedione | C7H11N3O2 | 详情 | 详情 | |
| (XII) | 37139 | 6-amino-5-nitroso-1-propyl-2,4(1H,3H)-pyrimidinedione | C7H10N4O3 | 详情 | 详情 | |
| (XIII) | 20546 | 5,6-diamino-1-propyl-2,4(1H,3H)-pyrimidinedione | C7H12N4O2 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(I)The esterification of cyanacetic acid (I) with 1-(diphenylmethyl)azetidin-3-ol (II) by means of dicyclohexylcarbodiimide (DCC) in hot THF gives the corresponding cyanacetic ester (III), which is treated with HCl and then with NH3 to afford amidinoacetic acid (1-diphenylmethyl)azetidin-3-yl ester (IV). Finally, this compound is cyclized with 2-(3-nitrobenzylidene)acetoacetic acid isopropyl ester (V) by means of sodium methoxide in refluxing isopropanol.
| 【1】 Koike, H.; Yoshimoto, M.; Nishino, H. (Sankyo Co., Ltd.; Ube Industries, Ltd.); Dihydropyridine derivs., their preparation and their use. EP 0266922; EP 0529702; JP 1988253082; US 4772596 . |
| 【2】 Prous, J.; Castaner, J.; CS-905. Drugs Fut 1990, 15, 7, 1671. |
| 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) | 12591 | Cyanoacetic Acid; 2-Cyanoacetic acid | 372-09-8 | C3H3NO2 | 详情 | 详情 |
| (II) | 12592 | 1-Benzhydryl-3-azetidinol; 1-Benzhydryl-3-hydroxyazetidine；1-benzhydrylazetidin-3-ol | 18621-17-5 | C16H17NO | 详情 | 详情 |
| (III) | 12593 | 1-benzhydryl-3-azetidinyl 2-cyanoacetate | C19H18N2O2 | 详情 | 详情 | |
| (IV) | 12594 | 1-benzhydryl-3-azetidinyl 3-amino-3-iminopropanoate | C19H21N3O2 | 详情 | 详情 | |
| (V) | 12595 | isopropyl (Z)-2-acetyl-3-(3-nitrophenyl)-2-propenoate | C14H15NO5 | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(II)The condensation of 2-chlorobenzoyl chloride (I) with cyanacetic acid (II) by means of butyllithium in THF gives 2-(2-chlorobenzoyl)acetonitrile (III), which is cyclized with N-(ethoxycarbonyl)piperidin-4-one (IV) by means of S and morpholine in refluxing methanol yielding the bicyclic ethyl ester (V). The acylation of (V) with bromoacetyl bromide (VI) in chloroform affords the corresponding 2-(bromoacetamido) derivative (VII), which by reaction with dry ammonia in THF is converted into the 2-glycinamido derivative (VIII). The cyclization of (VIII) in refluxing pyridine gives the tricyclic ethyl ester (IX), which by reaction with P2S5 in refluxing pyridine is converted into the corresponding thioketone (X). The reaction of (X) with hydrazine in methanol yields the 2-hydrazino derivative (XI), which is acylated with acetyl chloride (XII) and NaHCO3 in THF affording the 2-(acetylhydrazino) derivative (XIII). The cyclization of (XIII) in refluxing acetic acid gives the tetracyclic ethyl ester (XIV), which is decarboxylated with 30% HBr yielding the tetracyclic precursor (XV). The acylation of (XV) with 2-(3,4-dimethoxyphenylthio)acetic acid (XVI) by means of dicyclohexylcarbodiimide (DCC) in DMF affords the acylated compound (XVII), which is finally treated with P2S5 or Lawesson's reagent.
| 【1】 Braquet, P.; Esanu, A.; Laurent, J.-P.; Pommier, J. (SCRAS (Societé de Conseils de Recherches et d'Applications Scientifiques)); Thieno-triazolo-diazepine derivs. and process for their preparation. BE 1004122; CH 681009; DE 4015137; FR 2646774; FR 2646851; GB 2231330; JP 1991005484; US 5049559 . |
| 【2】 Braquet,P.; Castaner, J.; Duverger, D.; Koltai, M.; Spinnewyn, B.; Pirotzky, E.; Esanu, A.; BN 50739. Drugs Fut 1991, 16, 5, 413. |
| 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) | 14000 | o-Chlorobenzoyl chloride; 2-Chlorobenzoyl chloride | 609-65-4 | C7H4Cl2O | 详情 | 详情 |
| (II) | 12591 | Cyanoacetic Acid; 2-Cyanoacetic acid | 372-09-8 | C3H3NO2 | 详情 | 详情 |
| (III) | 12923 | 3-(2-Chlorophenyl)-3-oxopropanenitrile | 40018-25-5 | C9H6ClNO | 详情 | 详情 |
| (IV) | 13486 | Ethyl 4-oxo-1-piperidinecarboxylate; N-Carbethoxy-4-piperidone | 29976-53-2 | C8H13NO3 | 详情 | 详情 |
| (V) | 14004 | ethyl 2-amino-3-(2-chlorobenzoyl)-4,7-dihydrothieno[2,3-c]pyridine-6(5H)-carboxylate | C17H17ClN2O3S | 详情 | 详情 | |
| (VI) | 14005 | 2-Bromoacetyl bromide; Bromoacetyl bromide | 598-21-0 | C2H2Br2O | 详情 | 详情 |
| (VII) | 14006 | ethyl 2-[(2-bromoacetyl)amino]-3-(2-chlorobenzoyl)-4,7-dihydrothieno[2,3-c]pyridine-6(5H)-carboxylate | C19H18BrClN2O4S | 详情 | 详情 | |
| (VIII) | 14007 | ethyl 2-[(2-aminoacetyl)amino]-3-(2-chlorobenzoyl)-4,7-dihydrothieno[2,3-c]pyridine-6(5H)-carboxylate | C19H20ClN3O4S | 详情 | 详情 | |
| (IX) | 14008 | ethyl 5-(2-chlorophenyl)-2-oxo-1,2,3,6,7,9-hexahydro-8H-pyrido[4',3':4,5]thieno[2,3-e][1,4]diazepine-8-carboxylate | C19H18ClN3O3S | 详情 | 详情 | |
| (X) | 14009 | ethyl 5-(2-chlorophenyl)-2-thioxo-1,2,3,6,7,9-hexahydro-8H-pyrido[4',3':4,5]thieno[2,3-e][1,4]diazepine-8-carboxylate | C19H18ClN3O2S2 | 详情 | 详情 | |
| (XI) | 14010 | ethyl 5-(2-chlorophenyl)-2-hydrazino-3,6,7,9-tetrahydro-8H-pyrido[4',3':4,5]thieno[2,3-e][1,4]diazepine-8-carboxylate | C19H20ClN5O2S | 详情 | 详情 | |
| (XII) | 14011 | 1-(Chlorooxy)-1-oxoethane | C2H3ClO2 | 详情 | 详情 | |
| (XIII) | 14012 | ethyl 2-(2-acetylhydrazino)-5-(2-chlorophenyl)-3,6,7,9-tetrahydro-8H-pyrido[4',3':4,5]thieno[2,3-e][1,4]diazepine-8-carboxylate | C21H22ClN5O3S | 详情 | 详情 | |
| (XIV) | 14013 | ethyl 6-(2-chlorophenyl)-1-methyl-7,10-dihydro-4H-pyrido[4',3':4,5]thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine-9(8H)-carboxylate | C21H20ClN5O2S | 详情 | 详情 | |
| (XV) | 14014 | 6-(2-Chlorophenyl)-1-methyl-7,8,9,10-tetrahydro-4H-pyrido[4',3':4,5]thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine | C18H16ClN5S | 详情 | 详情 | |
| (XVI) | 14015 | 2-[(3,4-Dimethoxyphenyl)sulfanyl]acetic acid | 95735-63-0 | C10H12O4S | 详情 | 详情 |
| (XVII) | 14016 | 1-[6-(2-Chlorophenyl)-1-methyl-7,10-dihydro-4H-pyrido[4',3':4,5]thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-9(8H)-yl]-2-[(3,4-dimethoxyphenyl)sulfanyl]-1-ethanone | C28H26ClN5O3S2 | 详情 | 详情 |
合成路线4
该中间体在本合成路线中的序号：(III)N,N'-Bis(cyclopropylmethyl)urea (II) was prepared by the action of phosgene on cyclopropylmethylamine (I). Cyclization of urea (II) with cyanoacetic acid (III) in hot acetic anhydride produced the 6-aminouracil (IV). Subsequent nitrosation of (IV) by means of sodium nitrite and formic acid afforded the 5-nitroso derivative (V), which was further reduced to the 5,6-diaminouracil (VI) with sodium dithionite. Formylation of diamine (VI), followed by cyclization of the intermediate formamide (VII), gave rise to 1,3-bis(cyclopropylmethyl)xanthine (VIII). Nitration of xanthine (VIII) with HNO3 in acetic acid yielded the 8-nitro derivative (IX), which was finally reduced to the corresponding amine employing either tin and HCl or sodium dithionite.
| 【1】 Maschler, H.; Spicer, B.A.; Smith, H. (GlaxoSmithKline plc); Xanthine derivs., process for their preparation and their pharmaceutical use. AU 9052083; EP 0389282; EP 1120417; JP 1990273676; US 5734051; US 5981535; US 6180791; US 6531600 . |
| 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) | 59524 | Aminomethylcyclopropane; Cyclopropanemethylamine | 2516-47-4 | C4H9N | 详情 | 详情 |
| (II) | 59525 | N,N'-bis(cyclopropylmethyl)urea | C9H16N2O | 详情 | 详情 | |
| (III) | 12591 | Cyanoacetic Acid; 2-Cyanoacetic acid | 372-09-8 | C3H3NO2 | 详情 | 详情 |
| (IV) | 59526 | 6-amino-1,3-bis(cyclopropylmethyl)-2,4(1H,3H)-pyrimidinedione | C12H17N3O2 | 详情 | 详情 | |
| (V) | 59527 | 6-amino-1,3-bis(cyclopropylmethyl)-5-nitroso-2,4(1H,3H)-pyrimidinedione | C12H16N4O3 | 详情 | 详情 | |
| (VI) | 59528 | 5,6-diamino-1,3-bis(cyclopropylmethyl)-2,4(1H,3H)-pyrimidinedione | C12H18N4O2 | 详情 | 详情 | |
| (VII) | 59529 | 6-amino-1,3-bis(cyclopropylmethyl)-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinylformamide | C13H18N4O3 | 详情 | 详情 | |
| (VIII) | 59530 | 1,3-bis(cyclopropylmethyl)-3,7-dihydro-1H-purine-2,6-dione | C13H16N4O2 | 详情 | 详情 | |
| (IX) | 59531 | 1,3-bis(cyclopropylmethyl)-8-nitro-3,7-dihydro-1H-purine-2,6-dione | C13H15N5O4 | 详情 | 详情 |
合成路线5
该中间体在本合成路线中的序号：(II)Cyclization of N,N'-diethylurea (I) with cyanoacetic acid (II) in hot acetic anhydride gives 6-amino-1,3-diethyluracil (III) which is nitrosated with NaNO2/HOAc in water to yield 6-amino-1,3-diethyl-5-nitrosouracil (IV). The reduction of (IV) with Na2S2O4 and K2CO3 in concentrated aqueous ammonia affords 5,6-diamino-1,3-diethyluracil (V), which is condensed with either 3-(3,4-dimethoxyphenyl)-2(E)-propenoyl chloride (VI) in EtOH/water or 3-(3,4-dimethoxyphenyl)-2(E)-propenoic acid (VII) and 3-[3-(diethylamino)propyl]-1-ethylcarbodiimide (EDAC) in dioxane/water to provide the corresponding amide (VIII). Cyclization of (VIII) by means of NaOH in the same solvent furnishes the xanthine derivative (IX), which is finally methylated with methyl iodide and K2CO3 in DMF.
| 【1】 Blicke, F.F.; Godt, H.C. Jr.; Reactions of 1,3-dimethyl-5,6-diaminouracil. J Am Chem Soc 1954, 76, 2798. |
| 【2】 Leeson, P.A.; Castañer, J.; Sorbera, L.A.; Martín, L.; Rabasseda, X.; KW-6002. Drugs Fut 2001, 26, 1, 21. |
| 【3】 Shimada, J.; Koike, N.; Nonaka, H.; et al.; Adenosine A2A antagonists with potent anti-cataleptic activity. Bioorg Med Chem Lett 1997, 7, 18, 2349. |
| 【4】 Suzuki, F.; Shimada, J.; Ishii, A.; Nakamura, J.; Ichikawa, S.; Kitamura, S.; Koike, N. (Kyowa Hakko Kogyo Co., Ltd.); Antidepressant. EP 0628311; JP 1994502746; WO 9401114 . |
| 【5】 Suzuki, F.; Shimada, J.; Koike, N.; Nakamura, J.; Shiozaki, S.; Ichikawa, S.; Nonaka, H. (Kyowa Hakko Kogyo Co., Ltd.); Therapeutic agents for Parkinson's disease. EP 0590919; JP 1994211856; US 5484920 . |
| 【6】 Miwa, K.; Ito, K.; Kato, N.; Kuge, Y.; Kousai, M.; Tomioka, S. (Kyowa Hakko Kogyo Co., Ltd.); Preparation of uracil derivs.. JP 1997040652 . |
| 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) | 43818 | N,N'-diethylurea | 623-76-7 | C5H12N2O | 详情 | 详情 |
| (II) | 12591 | Cyanoacetic Acid; 2-Cyanoacetic acid | 372-09-8 | C3H3NO2 | 详情 | 详情 |
| (III) | 43819 | 6-amino-1,3-diethyl-2,4(1H,3H)-pyrimidinedione | C8H13N3O2 | 详情 | 详情 | |
| (IV) | 43820 | 6-amino-1,3-diethyl-5-nitroso-2,4(1H,3H)-pyrimidinedione | C8H12N4O3 | 详情 | 详情 | |
| (V) | 28567 | 5,6-diamino-1,3-diethyl-2,4(1H,3H)-pyrimidinedione | C8H14N4O2 | 详情 | 详情 | |
| (VI) | 33601 | (E)-3-(3,4-dimethoxyphenyl)-2-propenoyl chloride | C11H11ClO3 | 详情 | 详情 | |
| (VII) | 28568 | (E)-3-(3,4-dimethoxyphenyl)-2-propenoic acid | 2316-26-9 | C11H12O4 | 详情 | 详情 |
| (VIII) | 43821 | (E)-N-(6-amino-1,3-diethyl-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinyl)-3-(3,4-dimethoxyphenyl)-2-propenamide | C19H24N4O5 | 详情 | 详情 | |
| (IX) | 28569 | 8-[(E)-2-(3,4-dimethoxyphenyl)ethenyl]-1,3-diethyl-3,7-dihydro-1H-purine-2,6-dione | C19H22N4O4 | 详情 | 详情 |
合成路线6
该中间体在本合成路线中的序号：(VI)Condensation of p-fluorobenzaldehyde (I) with propionic anhydride (II) by means of sodium propionate at 140 C affords p-fluoro-alpha-methylcinnamic acid (III), which is then hydrogenated over Pd/C in EtOH to provide p-fluoro-alpha-methylhydrocinnamic acid (IV). Derivative (IV) is subjected to cyclization by treatment with polyphosphoric acid (PPA) to give 6-fluoro-2-methylindanone (V), which is converted into 5-fluoro-2-methylindenyl-3-acetic acid (VII) by first condensation with cyanoacetic acid (VI) by means of acetic acid and ammonium acetate in refluxing toluene, followed by hydrolysis with KOH in hot ethanol. Condensation of derivative (VII) with p-methylthiobenzaldehyde (VIII) by means of sodium methoxide in hot MeOH affords 5-fluoro-2-methyl-1-[p-(methylsulfanyl)benzylidene]-3-indenyl acetic acid (IX), which is then oxidized in MeOH/acetone by means of an aqueous solution of sodium periodate to yield methylsulfinylbenzylidene derivative (X). Finally, the target product is obtained by further oxidation of (X) with H2O2 in the presence of sodium methoxide and sodium bicarbonate in MeOH/acetonitrile at -10 C.
| 【1】 Mayle, M.J.; Menander, K.B. (Cell Pathways, Inc.); A method for treating patients with acne by administering a cyclic GMP PDE inhibitor. WO 0044372 . |
| 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) | 12337 | 4-fluorobenzaldehyde | 459-57-4 | C7H5FO | 详情 | 详情 |
| (II) | 20095 | propionic anhydride | 123-62-6 | C6H10O3 | 详情 | 详情 |
| (III) | 48870 | (Z)-3-(4-fluorophenyl)-2-methyl-2-propenoic acid | C10H9FO2 | 详情 | 详情 | |
| (IV) | 48871 | 3-(4-fluorophenyl)-2-methylpropionic acid | C10H11FO2 | 详情 | 详情 | |
| (V) | 48872 | 6-Fluoro-2-methylindanone | C10H9FO | 详情 | 详情 | |
| (VI) | 12591 | Cyanoacetic Acid; 2-Cyanoacetic acid | 372-09-8 | C3H3NO2 | 详情 | 详情 |
| (VII) | 48874 | 2-(5-fluoro-2-methyl-1H-inden-3-yl)acetic acid | C12H11FO2 | 详情 | 详情 | |
| (VIII) | 18815 | 4-(methylsulfanyl)benzaldehyde; 4-(methylmercapto)benzaldehyde | 3446-89-7 | C8H8OS | 详情 | 详情 |
| (IX) | 51940 | 2-(5-fluoro-2-methyl-1-[(E)-[4-(methylsulfanyl)phenyl]methylidene]-1H-inden-3-yl)acetic acid | C20H17FO2S | 详情 | 详情 | |
| (X) | 51941 | 2-(5-fluoro-2-methyl-1-[(E)-[4-(methylsulfinyl)phenyl]methylidene]-1H-inden-3-yl)acetic acid | C20H17FO3S | 详情 | 详情 |
合成路线7
该中间体在本合成路线中的序号：(IX)Sabcomeline can be obtained by several related ways: 1) The reaction of N-methoxyquinuclidine-3-carboxamide (I) with triphenylphosphine in refluxing CCl4 or with PCl5 in nitromethane gives N-methoxyquinuclidin-3-ylcarboxyimidoyl chloride (II), which by reaction with NaCN in hot DMSO is converted into 2-(methoxyimino)-2-(3-quinuclidinyl)acetonitrile (III). Finally, this compound is submitted to optical resolution with (R)-(-)-1,1'-binaphthyl-2,2'-diyl hydrogen phosphate [(R)-(-)-BNHP], or with 2,3:4,6-di-O-isopropylidene-2-oxo-L-gulonic acid [L-DIOG]. 2) The condensation of diethyl cyanomethylphosphonate (IV) with 3-quinuclidinone (V) by means of KOH in water gives 2-(quinuclidin-3-ylidene)acetonitrile (VI), which is hydrogenated with H2 over Pd/C in ethyl acetate to yield 2-(quinuclidin-3-yl)acetonitrile (VII). The nitrosation of (VII) with isoamyl nitrile and potassium tert-butoxide in THF affords 2-(hydroxyimino)-2-(3-quinuclidinyl)acetonitrile (VIII), which is methylated with methyl p-toluenesulfonate and potassium tert-butoxide in DMSO to give 2-(methoxyimino)-2-(3-quinuclidinyl)acetonitrile (III), already obtained. 3) The condensation of 3-quinuclidinone (V) with cyanacetic acid (IX) by means of NaOH in water gives 2-(quinuclidin-3-ylidene)cyanacetic acid (X), which is hydrogenated with H2 over Pd/C in water to yield 2-(3-quinuclidinyl)cyanacetic acid (XI). Finally, this compound is nitrosated with NaNO2/HCl to afford 2-(hydroxyimino)-2-(3-quinuclidinyl)acetonitrile (VIII), already obtained.
| 【1】 Graul, A.; Prous, J.; Castañer, J.; Sabcomeline Hydrochloride. Drugs Fut 1998, 23, 1, 41. |
| 【2】 Clark, M.S.G.; Bromidge, S.M.; Oriek,B.S.; Cassidy, F.; Eggleston, D.S.; Synthesis and properties of [R-(Z)]-(+)-alpha-(1-azabicyclo[2.2.2]oct-3-yl)-alpha-(methoxyimino) acetonitrile, a novel functionally selective muscarinic partial agonist. J Chem Soc Chem Commun 1994, 18, 18, 2189-90. |
| 【3】 Cassidy, F.; Bromidge, S.M.; Clark, M.S.G.; Brown, F.; Riley, G.J.; Dabbs, S.; Loudon, J.M.; Hawkins, J.; Orlek, B.S.; A novel and selective class of azabicyclic muscarinic agonists incorporating an N-methoxy imidoyl halide or nitrile functionality. Bioorg Med Chem Lett 1992, 2, 8, 791-6. |
| 【4】 Orlek, B.S.; Bromidge, S.M.; Dabbs, S. (SmithKline Beecham plc); Novel cpds. AU 9053159; EP 0392803; JP 1991007285; JP 1997188678; JP 1997188679; US 5278170 . |
| 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) | 16921 | N-methoxy-3-quinuclidinecarboxamide | C9H16N2O2 | 详情 | 详情 | |
| (II) | 16922 | N-methoxy-3-quinuclidinecarboximidoyl chloride | C9H15ClN2O | 详情 | 详情 | |
| (III) | 16923 | N-methoxy-3-quinuclidinecarboximidoyl cyanide | C10H15N3O | 详情 | 详情 | |
| (IV) | 10045 | Diethyl cyanomethylphosphonate | 2537-48-6 | C6H12NO3P | 详情 | 详情 |
| (V) | 16925 | 3-quinuclidinone; 1-azabicyclo[2.2.2]octan-3-one | 1193-65-3 | C7H11NO | 详情 | 详情 |
| (VI) | 16926 | 2-(1-azabicyclo[2.2.2]oct-3-ylidene)acetonitrile | C9H12N2 | 详情 | 详情 | |
| (VII) | 16927 | 2-(1-azabicyclo[2.2.2]oct-3-yl)acetonitrile | C9H14N2 | 详情 | 详情 | |
| (VIII) | 16928 | N-hydroxy-3-quinuclidinecarboximidoyl cyanide | C9H13N3O | 详情 | 详情 | |
| (IX) | 12591 | Cyanoacetic Acid; 2-Cyanoacetic acid | 372-09-8 | C3H3NO2 | 详情 | 详情 |
| (X) | 16930 | 2-(1-azabicyclo[2.2.2]oct-3-ylidene)-2-cyanoacetic acid | C10H12N2O2 | 详情 | 详情 | |
| (XI) | 16931 | 2-(1-azabicyclo[2.2.2]oct-3-yl)-2-cyanoacetic acid | C10H14N2O2 | 详情 | 详情 |
合成路线8
该中间体在本合成路线中的序号：(II)The cyclization of N-benzyl-N'-propylurea (I) with cyanacetic acid (II) in hot acetic anhydride gives 6-amino-1-benzyl-3-propyluracil (III), which is nitrosated with NaNO2/acetic acid and reduced with sodium dithionite to yield 5,6-diamino-1-benzyl-3-propyluracil (IV). The cyclization of (IV) with cyclopentylcarbonyl chloride (V) by means of NaOH in refluxing ethanol affords 3-benzyl-8-cyclopentyl-1-propylxanthine (VI), which is acylated with pivaloyl chloride (VII)/Na2CO3 in DMF giving the expected 7-acyl derivative (VIII). The debenzylation of (VIII) by hydrogenation over Pd/C as usual yields 8-cyclopentyl-7-pivaloyl-1-propylxanthine (IX), which is condensed with 1-bromo-3-fluoropropane (X) by means of Na2CO3 in DMF to afford 8-cyclopentyl-3-(3-fluoropropyl)-7-pivaloyl-1-propylxanthine (XI). Finally, this compound is deprotected with NaOH in DMSO/water.
| 【1】 Holschbach, M.H.; et al.; A1 adenosine receptor antagonists as ligands for positron emission tomography (PET) and single-photon emission tomography (SPET). J Med Chem 1998, 41, 4, 555. |
| 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) | 19803 | N-benzyl-N'-propylurea | C11H16N2O | 详情 | 详情 | |
| (II) | 12591 | Cyanoacetic Acid; 2-Cyanoacetic acid | 372-09-8 | C3H3NO2 | 详情 | 详情 |
| (III) | 19805 | 6-amino-1-benzyl-3-propyl-2,4(1H,3H)-pyrimidinedione | C14H17N3O2 | 详情 | 详情 | |
| (IV) | 19806 | 5,6-diamino-1-benzyl-3-propyl-2,4(1H,3H)-pyrimidinedione | C14H18N4O2 | 详情 | 详情 | |
| (V) | 19807 | 1,4-cyclopentadiene-1-carbonyl chloride | C6H5ClO | 详情 | 详情 | |
| (VI) | 19808 | 3-benzyl-8-cyclopentyl-1-propyl-3,7-dihydro-1H-purine-2,6-dione | C20H24N4O2 | 详情 | 详情 | |
| (VII) | 13597 | 2,2-Dimethylpropanoyl chloride; Pivaloyl chloride | 3282-30-2 | C5H9ClO | 详情 | 详情 |
| (VIII) | 19810 | 3-benzyl-8-cyclopentyl-7-(2,2-dimethylpropanoyl)-1-propyl-3,7-dihydro-1H-purine-2,6-dione | C25H32N4O3 | 详情 | 详情 | |
| (IX) | 19811 | 8-cyclopentyl-7-(2,2-dimethylpropanoyl)-1-propyl-3,7-dihydro-1H-purine-2,6-dione | C18H26N4O3 | 详情 | 详情 | |
| (X) | 19812 | 1-bromo-3-fluoropropane | 352-91-0 | C3H6BrF | 详情 | 详情 |
| (XI) | 19813 | 8-Cyclopentyl-3-(3-fluoropropyl)-7-pivaloyl-1-propylxanthine | C21H31FN4O3 | 详情 | 详情 |
合成路线9
该中间体在本合成路线中的序号：(II)Acylation of urea derivative (I) with cyanoacetic acid (II) in HOAc in the presence of Ac2O yields derivative (III), which is then cyclized by treatment with NaOH to provide (IV). Nitrosation of (IV) with NaNO2 and HCl affords nitroso derivative (V), which is then hydrogenated over Pd/C in EtOH to furnish substituted pyrimidinedione (VI). Finally, (VI) is coupled to Trolox (VII) with N-ethyl-N'-[3-(dimethylamino)propyl]carbodiimide hydrochloride (EDC·HCl) and 1-hydroxybenzotriazole (HOBt) in DMF or with 4-(dimethylamino)pyridine (DMAP) and N-dicyclohexylcarbodiimide (DCC) in CH2Cl2 to yield the target compound.
| 【2】 Isobe, Y.; Goto, Y.; Tobe, M.; Takahashi, O. (Japan Energy Corp.); Hydroquinone derivs. and their medicinal use. JP 1998147575; US 5821247 . |
| 【1】 Matsui, J.; Tsuchiya, M.; Hayashi, H.; Goto, Y.; Hirota, K.; Obara, f.; Isobe, Y.; Tobe, M.; Synthesis and biological evaluation of CX-659S and its related compounds for their inhibitory effects on the delayed-type hypersensitivity reaction. Bioorg Med Chem 2000, 8, 8, 2037. |
| 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) | 44181 | N-methyl-N'-phenylurea | 1007-36-9 | C8H10N2O | 详情 | 详情 |
| (II) | 12591 | Cyanoacetic Acid; 2-Cyanoacetic acid | 372-09-8 | C3H3NO2 | 详情 | 详情 |
| (III) | 44182 | N-(2-cyanoacetyl)-N-methyl-N'-phenylurea | C11H11N3O2 | 详情 | 详情 | |
| (IV) | 44183 | 6-amino-3-methyl-1-phenyl-2,4(1H,3H)-pyrimidinedione | C11H11N3O2 | 详情 | 详情 | |
| (V) | 44184 | 6-amino-3-methyl-5-nitro-1-phenyl-2,4(1H,3H)-pyrimidinedione | C11H10N4O4 | 详情 | 详情 | |
| (VI) | 44185 | 5,6-diamino-3-methyl-1-phenyl-2,4(1H,3H)-pyrimidinedione | C11H12N4O2 | 详情 | 详情 | |
| (VII) | 34833 | (2S)-6-hydroxy-2,5,7,8-tetramethyl-3,4-dihydro-2H-chromene-2-carboxylic acid | C14H18O4 | 详情 | 详情 |
合成路线10
该中间体在本合成路线中的序号：(II)The reaction of 4-hydroxybenzaldehyde (I) with cyanacetic acid (II) by means of pyridine in toluene gives the 3-(4-hydroxyphenyl)propenenitrile (III), which by reaction first with methanolic HCl and then with methanolic ammonia is converted into the amidine (IV). Finally, this compound is condensed with 2-furylcarbonyl chloride (V) in pyridine and treated with methanesulfonic acid to afford the target sulfonate.
| 【1】 Niwas, S.; Moore, R.; Kilpatrick, J.M.; Babu, Y.S.; Johnson, H.; Kellogg, D.; Development of novel inhibitors of complement and coagulation serine proteases. 216th ACS Natl Meet (Aug. 23-27, Boston) 1998, Abst MEDI 088. |
| 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) | 13433 | 4-Hydroxybenzaldehyde; p-Hydroxybenzaldehyde | 123-08-0 | C7H6O2 | 详情 | 详情 |
| (II) | 12591 | Cyanoacetic Acid; 2-Cyanoacetic acid | 372-09-8 | C3H3NO2 | 详情 | 详情 |
| (III) | 27819 | (E)-3-(4-hydroxyphenyl)-2-propenenitrile | C9H7NO | 详情 | 详情 | |
| (IV) | 27820 | (E)-3-(4-hydroxyphenyl)-2-propenimidamide | C9H10N2O | 详情 | 详情 | |
| (V) | 26093 | 2-Furoyl chloride | 527-69-5 | C5H3ClO2 | 详情 | 详情 |
合成路线11
该中间体在本合成路线中的序号：(V)Title compound has been prepared by two synthetic ways: 1) Condensation of the acetoacetanilide (I) with triethyl orthoformate in the presence of Ac2O provided the ethoxymethylene compound (II), which was reacted with hydroxylamine in methanol-water to afford isoxazole (III). Ring opening of the heterocycle with NaOH then gave the target cyanoacetanilide. 2) In a different procedure, cyanoacetic acid (V) was coupled with 2,5-dibromoaniline (IV) in the presence of diisopropyl carbodiimide (DIC) to form cyanoacetanilide (VI), which was acylated using acetyl chloride and NaH to afford the hydroxyethylidene derivative.
| 【1】 Ghosh, S.; Zheng, Y.; Jun, X.; Narla, R.K.; Mahajan, S.; Navara, C.; Mao, C.; Sudbeck, E.A.; Uckun, F.M.; alpha-Cyano-beta-hydroxy-beta-methyl-N-[4-(trifluoromethoxy)phenyl]propenamide: An inhibitor of the epidermal growth factor receptor tyrosine kinase with potent cytotoxic activity. Clin Cancer Res 1998, 4, 11, 2657. |
| 【2】 Ertel, H.; Wolf, E.; Heubach, G. (Aventis SA); Cyano acetic acid anilide derivs., process for their manufacture and compsns. containing these cpds.. DE 2524929; US 4061767 . |
| 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) | 21458 | N-(2,5-dibromophenyl)-3-oxobutanamide | C10H9Br2NO2 | 详情 | 详情 | |
| (II) | 21459 | (E)-2-acetyl-N-(2,5-dibromophenyl)-3-ethoxy-2-propenamide | C13H13Br2NO3 | 详情 | 详情 | |
| (III) | 21460 | N-(2,5-dibromophenyl)-5-methyl-4-isoxazolecarboxamide | C11H8Br2N2O2 | 详情 | 详情 | |
| (IV) | 21461 | 2,5-dibromoaniline; 2,5-dibromophenylamine | 3638-73-1 | C6H5Br2N | 详情 | 详情 |
| (V) | 12591 | Cyanoacetic Acid; 2-Cyanoacetic acid | 372-09-8 | C3H3NO2 | 详情 | 详情 |
| (VI) | 21463 | 2-cyano-N-(2,5-dibromophenyl)acetamide | C9H6Br2N2O | 详情 | 详情 |
合成路线12
该中间体在本合成路线中的序号：(I)Two synthetic ways have been reported for the compound. Coupling of cyanoacetic acid (II) to 4-(trifluoromethoxy)aniline (I) in the presence of diisopropylcarbodiimide formed the cyanoacetamide (III), which was treated with NaH and then acylated with acetyl chloride to yield the title compound.
| 【1】 Ghosh, S.; Zheng, Y.; Jun, X.; Narla, R.K.; Mahajan, S.; Navara, C.; Mao, C.; Sudbeck, E.A.; Uckun, F.M.; alpha-Cyano-beta-hydroxy-beta-methyl-N-[4-(trifluoromethoxy)phenyl]propenamide: An inhibitor of the epidermal growth factor receptor tyrosine kinase with potent cytotoxic activity. Clin Cancer Res 1998, 4, 11, 2657. |
| 【2】 Ghosh, S.; Uckun, F.M.; Zheng, Y. (Parker Hughes Institute); Inhibitors of the EGF-receptor tyrosine kinase and their use. WO 0056703 . |
合成路线13
该中间体在本合成路线中的序号：(I)Cyanoacetic acid (I) is condensed with urethane (II) in hot Ac2O to afford N ethoxycarbonyl-cyanoacetamide (III). Subsequent reaction of (III) with triethyl orthoformate yields alpha-cyano-beta-ethoxy-N-ethoxycarbonyl-acrylamide (IV). The ethoxy group of (IV) is then displaced with hydrazine hydrate in EtOH to produce the hydrazino acrylamide (V). Finally, thermal cyclization of (V) gives rise to the title pyrazolopyrimidine (1, 2).
| 【1】 Hildick, B.G.; Shaw, G.; Purines, pyrimidines, and imidazoles. Part XXXVII. Some new syntheses of pyrazolo[3,4-d]pyrimidines, including allopurinol. J Chem Soc 1971, 9, 1610. |
| 【2】 Shaw, G.; Baildon, S.; Lees, P. Sr.; Process for the preparation of biologically active cpds. as well as novel cpds.. DE 1814082 . |
| 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) | 12591 | Cyanoacetic Acid; 2-Cyanoacetic acid | 372-09-8 | C3H3NO2 | 详情 | 详情 |
| (II) | 24199 | Ethyl carbamate; Urethane | 51-79-6 | C3H7NO2 | 详情 | 详情 |
| (III) | 48249 | ethyl 2-cyanoacetylcarbamate | C6H8N2O3 | 详情 | 详情 | |
| (IV) | 63576 | ethyl (E)-2-cyano-3-ethoxy-2-propenoylcarbamate | C9H12N2O4 | 详情 | 详情 | |
| (V) | 63577 | ethyl (E)-2-cyano-3-hydrazino-2-propenoylcarbamate | C7H10N4O3 | 详情 | 详情 |
合成路线14
该中间体在本合成路线中的序号：(IV)5-Fluoroisatin (I) is alkylated with 4-methylbenzyl bromide (II) in the presence of NaH to afford the N-benzyl isatin derivative (III). Then, Knoevenagel condensation of isatin (III) with cyanoacetic acid (IV) by means of triethylamine in dioxane gives the indolinylidene adduct (V) as a mixture of E and Z isomers. Subsequent catalytic hydrogenation of (V) over Pd/C then furnishes the target compound
| 【1】 Da Settimo, F.; Primofiore, G.; Da Settimo, A.; La Motta, C.; Simorini, F.; Novellino, E.; Greco, G.; Lavecchia, A.; Boldrini, E.; Novel, highly potent aldose reductase inhibitors: Cyano(2-oxo-2,3-dihydroindol-3-yl)acetic acid derivatives. J Med Chem 2003, 46, 8, 1419. |
| 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) | 21552 | 5-fluoro-1H-indole-2,3-dione | 443-69-6 | C8H4FNO2 | 详情 | 详情 |
| (II) | 24623 | 1-(bromomethyl)-4-methylbenzene | 104-81-4 | C8H9Br | 详情 | 详情 |
| (III) | 63451 | thieno[3,2-b]pyridin-7(4H)-one | C7H5NOS | 详情 | 详情 | |
| (IV) | 12591 | Cyanoacetic Acid; 2-Cyanoacetic acid | 372-09-8 | C3H3NO2 | 详情 | 详情 |
| (V) | 63542 | 2-cyano-2-[5-fluoro-1-(4-methylbenzyl)-2-oxo-1,2-dihydro-3H-indol-3-ylidene]acetic acid | C19H13FN2O3 | 详情 | 详情 |
合成路线15
该中间体在本合成路线中的序号：(XIV)An enantioselective synthesis of the (3R,4R)-isomer has also been reported. Quaternization of 3-(methoxycarbonylamino)-4-methylpyridine (VII) with benzyl chloride in toluene at 80 °C, followed by reduction of the resulting pyridinium salt (VIII) with NaBH4 in ethanol, yields the tetrahydropyridine (IX). Enantioselective hydrogenation of (IX) in the presence of chiral rhodium catalyst in ethanol, and subsequent purification of the obtained piperidine by crystallization as the corresponding di-p-toluoyltartrate salt, provides the pure (3R,4R)-enantiomer (X). This is then condensed with 2,4-dichloro-7H-pyrrolo[2,3-d]pyrimidine (XI) by means of K2CO3 in boiling water to give the tertiary amine (XII), which is subjected to simultaneous debenzylation and dechlorination by means of H2 and Pd(OH)2/C to yield the deprotected piperidine (XIII) (2). This compound is finally condensed with cyanoacetyl chloride (VI) (prepared from cyanoacetic acid [XIV] and oxalyl chloride) by means of triethylamine in dichloromethane to obtain the chiral CP-690550 (2, 3). Scheme 2.
| 【2】 Hawkins, J.M., Makowski, T.M., Ruggeri, S.G., Rutherford, J.L., Urban, F.J. (Pfizer Products Inc.). Pyrrolo[2,3-d]pyrimidine derivatives; their intermediates and synthesis. JP 2007039455, WO 2007012953. |
| 【3】 Flanagan, M.E., Li, Z.J. (Pfizer, Inc.). Novel crystalline cpd. JP 2005511696, US 2003130292, WO 03048162. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (VI) | 65394 | cyanoacetyl chloride | C3H2ClNO | 详情 | 详情 | |
| (VII) | 65395 | 3-(methoxycarbonylamino)-4-methylpyridine | C8H10N2O2 | 详情 | 详情 | |
| (VIII) | 65396 | 1-benzyl-3-(methoxycarbonylamino)-4-methylpyridinium chloride | C15H17ClN2O2 | 详情 | 详情 | |
| (IX) | 65397 | C15H20N2O2 | 详情 | 详情 | ||
| (X) | 65398 | (3R,4R)-1-Benzyl-N,4-dimethylpiperidin-3-amine | 477600-70-7 | C14H22N2 | 详情 | 详情 |
| (XI) | 65399 | 2,4-dichloro-7H-pyrrolo[2,3-d]pyrimidine; 2,4-Dichloro-1H-pyrrolo[2,3-d]pyrimidine | 90213-66-4 | C6H3Cl2N3 | 详情 | 详情 |
| (XII) | 65400 | C20H24ClN5 | 详情 | 详情 | ||
| (XIII) | 65401 | N-Methyl-N-[(3R,4R)-4-methyl-3-piperidinyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine | 477600-74-1 | C13H19N5 | 详情 | 详情 |
| (XIV) | 12591 | Cyanoacetic Acid; 2-Cyanoacetic acid | 372-09-8 | C3H3NO2 | 详情 | 详情 |
合成路线16
该中间体在本合成路线中的序号：(XXI)Uracil intermediate (I) is obtained as follows. Condensation of 2-fluoro-4-iodophenyl isocyanate (XIII) with cyclopropylamine (XIV) in Et2O , or alternatively reaction of 2-fluoro-4-iodoaniline (XV) with CDI in the presence of Et3N in DMF, followed by condensation with cyclopropylamine (XIV) affords disubstituted urea (XVI). Cyclization of urea (XVI) is treated with malonic acid (XVII) in the presence of AcCl in Ac2O at 60 °C affords the pyrimidine trione (XVIII), which is chlorinated using POCl3 in the presence of PhNMe2 and a catalytic amount of H2O at 90 °C to provide a mixture of 6-chloropyrimidine (XIX) and the corresponding regioisomer. Finally, chloropyrimidine (XIX) is treated with methylamine (XX) in EtOH at 80 °C .
In an alternative procedure, acylation of urea (XVI) with cyanoacetic acid (XXI) by means of MsCl in DMF yields the N-(cyanoacetyl)urea (XXII), which cyclizes in aqueous NaOH at 80 °C to yield the amino-pyrimidine derivative (XXIII). Condensation of amine (XXIII) with dimethylformamide dimethylacetal (XXIV) in DMF affords formamidine (XXV), which is finally reduced using NaBH4 in EtOH/t-BuOH .
| 【2】 Sakai, T., Kawasaki, H., Abe, H. et al. (Japan Tobacco, Inc.). 5-Amino-2,4,7-trioxo-3,4,7,8-tetrahydro-2H-pyrido[2,3-d]pyrimidine derivatives and related compounds for the treatment of cancer. CN 101912400, EP 1761528, EP 1894932, EP 2298768, JP 2008201788, JP 2008501631, US 2006014768, US 7378423, US 2008312228, US 201024013, WO 2005121142. |
| 【1】 Abe, H., Kikuchi, S., Hayakawa, K. et al. Discovery of a highly potent and selective MEK inhibitor: GSK1120212 (JTP-7407 DMSO solvate). ACS Med Chem Lett 2011, 2(4): 320. |
| 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) | 68359 | 1-(2-fluoro-4-iodophenyl)-3-cyclopropyl-6-(methylamino)uracil;3-cyclopropyl-1-(2-fluoro-4-iodophenyl)-6-(methylamino)pyrimidine-2,4(1H,3H)-dione | C14H13FIN3O2 | 详情 | 详情 | |
| (XIII) | 68369 | 2-fluoro-4-iodophenyl isocyanate | C7H3FINO | 详情 | 详情 | |
| (XIV) | 12263 | Cyclopropylamine; Cyclopropanamine | 765-30-0 | C3H7N | 详情 | 详情 |
| (XV) | 63342 | 2-fluoro-4-iodoaniline; 2-fluoro-4-iodophenylamine | 29632-74-4 | C6H5FIN | 详情 | 详情 |
| (XVI) | 68370 | 1-cyclopropyl-3-(2-fluoro-4-iodophenyl)urea | C10H10FIN2O | 详情 | 详情 | |
| (XVII) | 12963 | Malonic acid | 141-82-2 | C3H4O4 | 详情 | 详情 |
| (XVIII) | 68371 | 1-cyclopropyl-3-(2-fluoro-4-iodophenyl)pyrimidine-2,4,6(1H,3H,5H)-trione | C13H10FIN2O3 | 详情 | 详情 | |
| (XIX) | 68372 | 6-chloro-3-cyclopropyl-1-(2-fluoro-4-iodophenyl)pyrimidine-2,4(1H,3H)-dione | C13H9ClFIN2O2 | 详情 | 详情 | |
| (XX) | 11021 | Methanamine; Methylamine | 74-89-5 | CH5N | 详情 | 详情 |
| (XXI) | 12591 | Cyanoacetic Acid; 2-Cyanoacetic acid | 372-09-8 | C3H3NO2 | 详情 | 详情 |
| (XXII) | 68373 | 2-cyano-N-cyclopropyl-N-((2-fluoro-4-iodophenyl)carbamoyl)acetamide | C13H11FIN3O2 | 详情 | 详情 | |
| (XXIII) | 68374 | 6-amino-3-cyclopropyl-1-(2-fluoro-4-iodophenyl)pyrimidine-2,4(1H,3H)-dione | C13H11FIN3O2 | 详情 | 详情 | |
| (XXIV) | 11984 | N-(Dimethoxymethyl)-N,N-dimethylamine;dimethylformamide dimethylacetal;1,1-dimethoxy-N,N-dimethylmethanamine； Dimethoxy-N,N-dimethylmethanamine; N,N-Dimethylformamide dimethyl acetal | 4637-24-5 | C5H13NO2 | 详情 | 详情 |
| (XXV) | 68375 | (E)-N'-(1-cyclopropyl-3-(2-fluoro-4-iodophenyl)-2,6-dioxo-1,2,3,6-tetrahydropyrimidin-4-yl)-N,N-dimethylformimidamide | C16H16FIN4O2 | 详情 | 详情 |