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【结 构 式】 
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【分子编号】41353 【品名】(2R)-2-[[(benzyloxy)carbonyl]amino]-5-(tert-butoxy)-5-oxopentanoic acid 【CA登记号】3886-08-6 |
【 分 子 式 】C17H23NO6 【 分 子 量 】337.37276 【元素组成】C 60.52% H 6.87% N 4.15% O 28.45% |
合成路线1
该中间体在本合成路线中的序号：(XIV)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 |