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【结 构 式】

【分子编号】41360

【品名】tert-butyl (2S)-2-[[(benzyloxy)carbonyl]amino]-5-[[(1R)-4-(tert-butoxy)-4-oxo-1-(1H-1,2,3,4-tetraazol-5-yl)butyl]amino]-5-oxopentanoate

【CA登记号】

【 分 子 式 】C26H38N6O7

【 分 子 量 】546.62396

【元素组成】C 57.13% H 7.01% N 15.37% O 20.49%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号:(XXI)

N-(Benzyloxycarbonyl)-D-glutamic acid (XIV) was converted to the mixed anhydride (XV) with isobutyl chloroformate and then treated with ammonia to give amide (XVI). Dehydration of the amide with POCl3/pyridine produced nitrile (XVII) and further dipolar cycloaddition of NaN3 produced the tetrazole (XVIII). After hydrogenolysis of the benzyloxycarbonyl protecting group of (XVIII), the resulting amine (XIX) was coupled with N-(benzyloxycarbonyl)-L-glutamic acid (XX) via activation as the mixed anhydride with isobutyl chloroformate to give (XXI). The benzyloxycarbonyl group of (XXI) was then deprotected by catalytic hydrogenolysis over Pd/C as above, yielding amine (XXII). This was coupled with the intermediate benzoic acid derivative (XIII) employing benzotriazolyloxy-tris(pyrrolidino)phosphonium hexafluorophosphate to furnish amide (XXIII). The tert-butyl esters of (XXIII) were finally cleaved by treatment with trifluoroacetic acid.

1 Bavetsias, V.; Boyle, F.T.; Hennequin, L.F.A.; Marriott, J.H. (AstraZeneca plc; BTG plc); Anti-cancer cpds. containing cyclopentaquinazoline ring. EP 0758328; GB 2290082; JP 1997512812; US 5747499; WO 9530673 .
2 Jackman, A.L.; Melin, C.; Bavetsias, V.; Matusiak, Z.S.; Marriott, J.H.; Kimbel, C.; Boyle, F.T.; Design and synthesis of cyclopenta[g]quinazoline-based antifolates as inhibitors of thymidylate synthase and potential antitumor agents. J Med Chem 2000, 43, 10, 1910.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(XIII) 41349 4-[(2-methyl-4-oxo-4,6,7,8-tetrahydro-3H-cyclopenta[g]quinazolin-6-yl)(2-propynyl)amino]benzoic acid C22H19N3O3 详情 详情
(XIV) 41353 (2R)-2-[[(benzyloxy)carbonyl]amino]-5-(tert-butoxy)-5-oxopentanoic acid 3886-08-6 C17H23NO6 详情 详情
(XV) 41354   C22H31NO8 详情 详情
(XVI) 41355 tert-butyl (4R)-5-amino-4-[[(benzyloxy)carbonyl]amino]-5-oxopentanoate C17H24N2O5 详情 详情
(XVII) 41356 tert-butyl (4R)-4-[[(benzyloxy)carbonyl]amino]-4-cyanobutanoate C17H22N2O4 详情 详情
(XVIII) 41357 tert-butyl (4R)-4-[[(benzyloxy)carbonyl]amino]-4-(1H-1,2,3,4-tetraazol-5-yl)butanoate C17H23N5O4 详情 详情
(XIX) 41358 tert-butyl (4R)-4-amino-4-(1H-1,2,3,4-tetraazol-5-yl)butanoate C9H17N5O2 详情 详情
(XX) 41359 (4S)-4-[[(benzyloxy)carbonyl]amino]-5-(tert-butoxy)-5-oxopentanoic acid C17H23NO6 详情 详情
(XXI) 41360 tert-butyl (2S)-2-[[(benzyloxy)carbonyl]amino]-5-[[(1R)-4-(tert-butoxy)-4-oxo-1-(1H-1,2,3,4-tetraazol-5-yl)butyl]amino]-5-oxopentanoate C26H38N6O7 详情 详情
(XXII) 41361 tert-butyl (2S)-2-amino-5-[[(1R)-4-(tert-butoxy)-4-oxo-1-(1H-1,2,3,4-tetraazol-5-yl)butyl]amino]-5-oxopentanoate C18H32N6O5 详情 详情
(XXIII) 41362 tert-butyl (2S)-5-[[(1R)-4-(tert-butoxy)-4-oxo-1-(1H-1,2,3,4-tetraazol-5-yl)butyl]amino]-2-([4-[(2-methyl-4-oxo-4,6,7,8-tetrahydro-3H-cyclopenta[g]quinazolin-6-yl)(2-propynyl)amino]benzoyl]amino)-5-oxopentanoate C40H49N9O7 详情 详情
Extended Information