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【结 构 式】

【分子编号】56829

【品名】(2S)-2-{[4-({(2S)-2-amino-3-[(2,5-diamino-6-oxo-3,6-dihydro-4-pyrimidinyl)amino]propyl}amino)benzoyl]amino}pentanedioic acid

【CA登记号】

【 分 子 式 】C19H26N8O6

【 分 子 量 】462.46576

【元素组成】C 49.35% H 5.67% N 24.23% O 20.76%

与该中间体有关的原料药合成路线共 2 条

合成路线1

该中间体在本合成路线中的序号:(XX)

In a different synthetic strategy, L-serine methyl ester (X) was protected as the N-benzyl derivative (XI) by reductive alkylation with benzaldehyde and NaBH4. Ammonolysis of ester (XI) then produced N-benzyl serinamide (XII). Subsequent reduction of the amide function of (XII) employing borane-dimethyl sulfide complex gave diamine (XIII). This was condensed with the chloropyrimidine (XIV) to afford adduct (XV). After protection of the exocyclic amine with di-tert-butyl dicarbonate, alcohol (XVI) oxidation with Dess-Martin periodinane reagent yielded aldehyde (XVII). Reductive coupling of (XVII) with p-aminobenzoyl glutamic acid (XVIII), followed by acidic Boc group deprotection, led to the triaminopropane derivative (XIX). Catalytic hydrogenation of the nitro group of (XIX) and N-debenzylation over Pd/C yielded the pteridine ring precursor (XX).

1 Bailey, S.W.; et al.; Synthesis of tetrahydropteridine C6-stereoisomers, including N5-formyl-(6S)-tetrahydrofolic acid. J Org Chem 1992, 57, 16, 4470.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(X) 20915 methyl (2S)-2-amino-3-hydroxypropanoate 5680-80-8 C4H9NO3 详情 详情
(XI) 56820 methyl (2S)-2-(benzylamino)-3-hydroxypropanoate C11H15NO3 详情 详情
(XII) 56821 (2S)-2-(benzylamino)-3-hydroxypropanamide C10H14N2O2 详情 详情
(XIII) 56822 (2R)-3-amino-2-(benzylamino)-1-propanol C10H16N2O 详情 详情
(XIV) 56823 2-amino-6-chloro-5-nitro-4(1H)-pyrimidinone C4H3ClN4O3 详情 详情
(XV) 56824 2-amino-6-{[(2R)-2-(benzylamino)-3-hydroxypropyl]amino}-5-nitro-4(1H)-pyrimidinone C14H18N6O4 详情 详情
(XVI) 56825 tert-butyl (1R)-2-[(2-amino-5-nitro-6-oxo-3,6-dihydro-4-pyrimidinyl)amino]-1-(hydroxymethyl)ethyl(benzyl)carbamate C19H26N6O6 详情 详情
(XVII) 56826 tert-butyl (1R)-2-[(2-amino-5-nitro-6-oxo-3,6-dihydro-4-pyrimidinyl)amino]-1-formylethyl(benzyl)carbamate C19H24N6O6 详情 详情
(XVIII) 56827 (2S)-2-[(4-aminobenzoyl)amino]pentanedioic acid C12H14N2O5 详情 详情
(XIX) 56828 (2S)-2-[(4-{[(2S)-3-[(2-amino-5-nitro-6-oxo-3,6-dihydro-4-pyrimidinyl)amino]-2-(benzylamino)propyl]amino}benzoyl)amino]pentanedioic acid C26H30N8O8 详情 详情
(XX) 56829 (2S)-2-{[4-({(2S)-2-amino-3-[(2,5-diamino-6-oxo-3,6-dihydro-4-pyrimidinyl)amino]propyl}amino)benzoyl]amino}pentanedioic acid C19H26N8O6 详情 详情

合成路线2

该中间体在本合成路线中的序号:(XX)

Oxidation of the triamino pyrimidinone system (XX) by means of iodine produced the intermediate ortho-iminoquinone (XXI), which underwent hydrolysis to dione (XXII). Subsequent cyclization of (XXII) under controlled conditions led to the chiral tetrahydrofolic acid (VI). Finally, regioselective N5-formylation of (VI) was accomplished by treatment with formic acid and carbonyl diimidazole.

1 Bailey, S.W.; et al.; Synthesis of tetrahydropteridine C6-stereoisomers, including N5-formyl-(6S)-tetrahydrofolic acid. J Org Chem 1992, 57, 16, 4470.
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) 56817 (2S)-2-{[4-({[(6S)-2-amino-4-oxo-1,4,5,6,7,8-hexahydro-6-pteridinyl]methyl}amino)benzoyl]amino}pentanedioic acid C19H23N7O6 详情 详情
(XX) 56829 (2S)-2-{[4-({(2S)-2-amino-3-[(2,5-diamino-6-oxo-3,6-dihydro-4-pyrimidinyl)amino]propyl}amino)benzoyl]amino}pentanedioic acid C19H26N8O6 详情 详情
(XXI) 56830 (2S)-2-{[4-({(2S)-2-amino-3-[(2-amino-5-imino-6-oxo-5,6-dihydro-4-pyrimidinyl)amino]propyl}amino)benzoyl]amino}pentanedioic acid C19H24N8O6 详情 详情
(XXII) 56831 (2S)-2-{[4-({(2S)-2-amino-3-[(2-amino-5,6-dioxo-5,6-dihydro-4-pyrimidinyl)amino]propyl}amino)benzoyl]amino}pentanedioic acid C19H23N7O7 详情 详情
Extended Information