|
【结 构 式】 
|
【分子编号】44767 【品名】5-[4-[(5-methoxy-3-methyl-3H-imidazo[4,5-b]pyridin-2-yl)methoxy]benzyl]-3-trityl-1,3-thiazolidine-2,4-dione 【CA登记号】 |
【 分 子 式 】C38H32N4O4S 【 分 子 量 】640.76264 【元素组成】C 71.23% H 5.03% N 8.74% O 9.99% S 5% |
合成路线1
该中间体在本合成路线中的序号：(VII)Selective substitution of the 2-chloro group of 2,6-dichloro-3-nitropyridine (I) by methylamine gave 6-chloro-2-(methylamino)-3-nitropyridine (II). The 6-chloro group of (II) was then displaced by sodium methoxide to afford methyl ether (III). The nitro group of (III) was reduced by catalytic hydrogenation, and the resulting diamine (IV) was cyclized with glycolic acid to furnish the imidazopyridine (V). Mitsunobu coupling of alcohol (V) with 5-(4-hydroxybenzyl)-3-triphenylmethylthiazolidine-2,4-dione (VI) produced the corresponding ether (VII). The title compound was then obtained by acid deprotection of the trityl group of (VII), followed by conversion to the hydrochloride salt.
| 【2】 Wada, K.; Oguchi, M.; Honma, H.; et al.; Molecular design, synthesis, and hypoglycemic activity of a series of thiazolidine-2,4-diones. J Med Chem 2000, 43, 16, 3052. |
| 【1】 Fujita, T.; Fujimoto, K.; Yoshioka, T.; Yanagisawa, H.; Fujiwara, T.; Horikoshi, H.; Oguchi, M.; Wada, K. (Sankyo Co., Ltd.); Heterocyclic cpds. having antidiabetic activity, their preparation and their use. CA 2146701; EP 0676398; JP 1995330728; US 5624935; US 5834501; US 5962470; US 6117893 . |
| 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) | 13574 | 2,6-Dichloro-3-nitropyridine | 16013-85-7 | C5H2Cl2N2O2 | 详情 | 详情 |
| (II) | 44762 | N-(6-chloro-3-nitro-2-pyridinyl)-N-methylamine; 6-chloro-N-methyl-3-nitro-2-pyridinamine | C6H6ClN3O2 | 详情 | 详情 | |
| (III) | 44763 | 6-methoxy-N-methyl-3-nitro-2-pyridinamine; N-(6-methoxy-3-nitro-2-pyridinyl)-N-methylamine | C7H9N3O3 | 详情 | 详情 | |
| (IV) | 44764 | N-(3-amino-6-methoxy-2-pyridinyl)-N-methylamine; 6-methoxy-N(2)-methyl-2,3-pyridinediamine | C7H11N3O | 详情 | 详情 | |
| (V) | 44765 | (5-methoxy-3-methyl-3H-imidazo[4,5-b]pyridin-2-yl)methanol | C9H11N3O2 | 详情 | 详情 | |
| (VI) | 18803 | 5-(4-hydroxybenzyl)-3-trityl-1,3-thiazolidine-2,4-dione | C29H23NO3S | 详情 | 详情 | |
| (VII) | 44767 | 5-[4-[(5-methoxy-3-methyl-3H-imidazo[4,5-b]pyridin-2-yl)methoxy]benzyl]-3-trityl-1,3-thiazolidine-2,4-dione | C38H32N4O4S | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(II)Synthetic pathway for obtaining EN 292685: Treatment of amino acid (I) with CbzOSu affords the protected amino acid (II), which is further protected by means of Boc2O to yield derivative (III). Condensation of amino acid (III) with N,O-dimethyl hydroxylamine by means of BOP and DIEA provides hydroxamic ester (IV), which is then subjected to hydrogenolysis over Pd/C in CHCl3 for selective deprotection, furnishing compound (V). Coupling of (V) to intermediate (VI) affords derivative (VII), which is then coupled to lithium derivative (VIII) to give protected compound (IX). Finally, the Boc group of (IX) is removed by treatment with TFA.
| 【1】 Soll, R.M.; Lu, T.; Tomczuk, B.E.; Spurlino, J.; Pan, W.; Bone, R.; Green, D.W.; Heteroaryl keto thrombin inhibitors: Design and synthesis. 220th ACS Natl Meet (Aug 20 2000, Washington DC) 2000, Abst MEDI 285. |
| 【2】 Tumczuk, B.E.; Pan, W.; Soll, R.M.; Lu, T. (3-Dimensional Pharmaceuticals, Inc.); Heteroaryl protease inhibitors and diagnostic imaging agents. WO 0104117 . |
| 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) | 44766 | (2S)-2-amino-4-([[amino(imino)methyl]amino]oxy)butyric acid | C5H12N4O3 | 详情 | 详情 | |
| (II) | 44767 | 5-[4-[(5-methoxy-3-methyl-3H-imidazo[4,5-b]pyridin-2-yl)methoxy]benzyl]-3-trityl-1,3-thiazolidine-2,4-dione | C38H32N4O4S | 详情 | 详情 | |
| (III) | 44775 | (11S)-11-[[(benzyloxy)carbonyl]amino]-6-imino-2,2-dimethyl-4-oxo-3,8-dioxa-5,7-diazadodecan-12-oic acid | C18H26N4O7 | 详情 | 详情 | |
| (IV) | 44776 | benzyl (1S)-6-imino-1-[[methoxy(methyl)amino]carbonyl]-10,10-dimethyl-8-oxo-4,9-dioxa-5,7-diazaundec-1-ylcarbamate | C20H31N5O7 | 详情 | 详情 | |
| (V) | 44785 | tert-butyl (6S)-6-amino-8-methyl-7-oxo-3,9-dioxa-2,8-diazadec-1-animidoylcarbamate | C12H25N5O5 | 详情 | 详情 | |
| (VI) | 44786 | 2-[3-[[(2-iodobenzyl)sulfonyl]amino]-6-methyl-2-oxo-1(2H)-pyridinyl]acetic acid | C15H15IN2O5S | 详情 | 详情 | |
| (VII) | 44787 | tert-butyl (6S)-6-([2-[3-[[(2-iodobenzyl)sulfonyl]amino]-6-methyl-2-oxo-1(2H)-pyridinyl]acetyl]amino)-8-methyl-7-oxo-3,9-dioxa-2,8-diazadec-1-animidoylcarbamate | C27H38IN7O9S | 详情 | 详情 | |
| (VIII) | 23162 | 1,3-thiazol-2-yllithium | C3H2LiNS | 详情 | 详情 | |
| (IX) | 44788 | tert-butyl imino([[(3S)-3-([2-[3-[[(2-iodobenzyl)sulfonyl]amino]-6-methyl-2-oxo-1(2H)-pyridinyl]acetyl]amino)-4-oxo-4-(1,2lambda(5),3-thiadiazol-2-yl)butyl]oxy]amino)methylcarbamate | C27H35IN8O8S2 | 详情 | 详情 |