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【结 构 式】 
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【分子编号】44213 【品名】tert-butyl (1S)-2-[[(4aS,5R)-2-benzyl-1,3-dioxooctahydro-1H-pyrido[1,2-c]pyrimidin-5-yl]amino]-1-(1H-indol-3-ylmethyl)-2-oxoethylcarbamate 【CA登记号】 |
【 分 子 式 】C31H37N5O5 【 分 子 量 】559.66548 【元素组成】C 66.53% H 6.66% N 12.51% O 14.29% |
合成路线1
该中间体在本合成路线中的序号：(VIII)Condensation of Boc-D-Orn(COOCH2Ph)-OH (I) with the lithium salt of ethyl acetate (A) in the presence of CDI in THF affords derivative (II), which is then hydrogenated over Pd/C to yield the mixture of isomers (IIIa-b). Condensation of (IIIa-b) with benzyl isocyanate in THF, followed by simultaneous reduction and cyclization by means of NaH in THF, provides 1,3-dioxoperhydropyrido[1,2-c]pyrimidine (Va-b), whose N-Boc group is removed by treatment with TFA in CH2Cl2 to furnish amine (VI). Coupling of (VIa-b) to Boc-L-Trp-OH (VII) by means of BOP and Et3N in CH2Cl2, followed by chromatographic separation, gives derivative (VIII), which is subjected to Boc removal by treatment with TFA in CH2Cl2 to provide amine (IX). Finally, amine (IX) is condensed with t-butyl isocyanate in the presence of Et3N in THF to yield the target compound.
| 【1】 Martin-Martinez, M.; et al.; Synthesis and stereochemical structure-activity relationships of 1,3-dioxoperhydropyrido[1, 2-c]pyrimidine derivatives: Potent and selective cholecystokinin-A receptor antagonists. J Med Chem 1997, 40, 21, 3402. |
| 【2】 Bartolomé-Nebreda, J.M.; Gómez-Monterrey, I.; García-López, M.T.; González-Muñiz, R.; Martín-Martinez, M.; Ballaz, S.; Cenarruzabeitia, E.; LaTorre, M.; Del Rio, J.; Herranz, R.; 5-(Tryptophyl)amino-1,3-dioxoperhydropyrido[1,2-c]pyrimidine-based potent and selective CCK1 receptor antagonists: Structural modifications at the tryptophan domain. J Med Chem 1999, 42, 22, 4659. |
| 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) | 44205 | (2-ethoxy-2-oxoethyl)lithium | C4H7LiO2 | 详情 | 详情 | |
| (IIIa) | 44207 | ethyl 2-[(2R,3R)-3-[(tert-butoxycarbonyl)amino]piperidinyl]acetate | C14H26N2O4 | 详情 | 详情 | |
| (IIIb) | 44208 | ethyl 2-[(2S,3R)-3-[(tert-butoxycarbonyl)amino]piperidinyl]acetate | C14H26N2O4 | 详情 | 详情 | |
| (Va) | 44209 | tert-butyl (4aR,5R)-2-benzyl-1,3-dioxooctahydro-1H-pyrido[1,2-c]pyrimidin-5-ylcarbamate | C20H27N3O4 | 详情 | 详情 | |
| (Vb) | 44210 | tert-butyl (4aS,5R)-2-benzyl-1,3-dioxooctahydro-1H-pyrido[1,2-c]pyrimidin-5-ylcarbamate | C20H27N3O4 | 详情 | 详情 | |
| (VIa) | 44211 | (4aR,5R)-5-amino-2-benzylhexahydro-1H-pyrido[1,2-c]pyrimidine-1,3(2H)-dione | C15H19N3O2 | 详情 | 详情 | |
| (VIb) | 44212 | (4aS,5R)-5-amino-2-benzylhexahydro-1H-pyrido[1,2-c]pyrimidine-1,3(2H)-dione | C15H19N3O2 | 详情 | 详情 | |
| (I) | 44215 | (2R)-5-[[(benzyloxy)carbonyl]amino]-2-[(tert-butoxycarbonyl)amino]pentanoic acid | C18H26N2O6 | 详情 | 详情 | |
| (II) | 44206 | ethyl (4R)-7-[[(benzyloxy)carbonyl]amino]-4-[(tert-butoxycarbonyl)amino]-3-oxoheptanoate | C22H32N2O7 | 详情 | 详情 | |
| (IV) | 16730 | 1-(Isocyanatomethyl)benzene; Benzyl Isocyanate | 3173-56-6 | C8H7NO | 详情 | 详情 |
| (VII) | 16114 | N-alpha-t-BOC-L-tryptophan; (2S)-2-[(tert-butoxycarbonyl)amino]-3-(1H-indol-3-yl)propionic acid | 13139-14-5 | C16H20N2O4 | 详情 | 详情 |
| (VIII) | 44213 | tert-butyl (1S)-2-[[(4aS,5R)-2-benzyl-1,3-dioxooctahydro-1H-pyrido[1,2-c]pyrimidin-5-yl]amino]-1-(1H-indol-3-ylmethyl)-2-oxoethylcarbamate | C31H37N5O5 | 详情 | 详情 | |
| (IX) | 44214 | (2S)-N-[(4aS,5R)-2-benzyl-1,3-dioxooctahydro-1H-pyrido[1,2-c]pyrimidin-5-yl]-2-amino-3-(1H-indol-3-yl)propanamide | C26H29N5O3 | 详情 | 详情 | |
| (X) | 16976 | tert-butylisocyanate; tert-butyl isocyanate; 2-isocyanato-2-methylpropane | 1609-86-5 | C5H9NO | 详情 | 详情 |