Phenylalanine -Drug Synthesis Database

【结构式】

【分子编号】26219

【品名】Phenylalanine

【CA登记号】150-30-1

【分子式】C₉H₁₁NO₂

【分子量】165.19188

【元素组成】C 65.44% H 6.71% N 8.48% O 19.37%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(I)

Pictet-Spengler condensation of phenylalanine (I) with formaldehyde and HCl provided tetrahydroisoquinoline (II). Reduction of the carboxylic acid (II) to alcohol (III) was then performed in the presence of borane and BF3-Et2O. Subsequent protection of amino and hydroxyl groups of (III) with carbonyl diimidazole in boiling THF produced the cyclic carbamate (IV). After chlorosulfonation of (IV), the resulting sulfonyl chloride (V) was treated with ammonia in acetonitrile to furnish sulfonamide (VI). Finally, basic hydrolysis of the oxazolidinone (VI), followed by acid decarboxylation yielded the title compound.

参考文献中间体

合成目标

【1】 Teoh, B.; Dahanukar, V.H.; Criscione, K.R.; Grunewald, G.L.; 3,7-Disubstituted-1,2,3,4-tetrahydroisoquinolines display remarkable potency and selectivity as inhibitors of phenylethanolamine N-methyltransferase versus the alpha2-Adrenoceptor1a. J Med Chem 1999, 42, 11, 1982.

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)	26219	Phenylalanine	150-30-1	C₉H₁₁NO₂	详情	详情
(II)	26220	1,2,3,4-tetrahydro-3-isoquinolinecarboxylic acid	67123-97-1	C₁₀H₁₁NO₂	详情	详情
(III)	26221	1,2,3,4-tetrahydro-3-isoquinolinylmethanol		C₁₀H₁₃NO	详情	详情
(IV)	26222	1,5,10,10a-tetrahydro[1,3]oxazolo[3,4-b]isoquinolin-3-one		C₁₁H₁₁NO₂	详情	详情
(V)	26223	3-oxo-1,5,10,10a-tetrahydro[1,3]oxazolo[3,4-b]isoquinoline-7-sulfonyl chloride		C₁₁H₁₀ClNO₄S	详情	详情
(VI)	26224	3-oxo-1,5,10,10a-tetrahydro[1,3]oxazolo[3,4-b]isoquinoline-7-sulfonamide		C₁₁H₁₂N₂O₄S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XI)

Acylation of phenylalanine (XI) with benzoyl chloride (XII) under Schotten-Baumann conditions produced the corresponding benzamide (XIII). The cyclization of benzoylphenylalanine (XIII) in the presence of acetic anhydride afforded oxazolone (XIV), which was then reacted with trifluoroacetic anhydride producing the trifluoromethyl ketone (XV). After ketone (XV) reduction to carbinol (XVI) with NaBH4, the acidic hydrolysis of the benzamido group of (XVI) yielded the amino alcohol (XVII) (1). Condensation of acid (X) with amine (XVII) using EDC and HOBt gave amide (XVIII). The hydroxyl group of (XVIII) was then oxidized to ketone (XIX) employing a modified Pfitzner-Moffatt oxidation. Finally, hydrogenolysis of the benzyloxycarbonyl group of (XIX) furnished the desired aminopyrimidinone.

参考文献中间体

合成目标

【1】 Akahoshi, F.; Ashimori, A.; Yoshimura, T.; et al.; Non-peptidic inhibitors of human chymase. Synthesis, structure-activity relationships, and pharmacokinetic profiles of a series of 5-amino-6-oxo-1,6-dihydropyrimidine-containing trifluoromethyl ketones. Bioorg Med Chem 2001, 9, 2, 301.
【2】 Akahoshi, F.; Yoshimura, T.; Eda, M.; Ashimori, A.; Fukuyama, H.; Nakajima, M.; Imada, T.; Okunishi, H.; Miyazaki, M. (Welfide Corporation); Heterocyclic amide cpds. and medicinal use of the same. EP 0826671; US 5948785; WO 9633974 .

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)	49080	2-[5-[[(benzyloxy)carbonyl]amino]-2-(4-fluorophenyl)-6-oxo-1(6H)-pyrimidinyl]acetic acid		C₂₀H₁₆FN₃O₅	详情	详情
(XI)	26219	Phenylalanine	150-30-1	C₉H₁₁NO₂	详情	详情
(XII)	10463	Benzoyl chloride	98-88-4	C₇H₅ClO	详情	详情
(XIII)	49081	N-Benzoyl-DL-phenylalanine	2901-76-0	C₁₆H₁₅NO₃	详情	详情
(XIV)	49082	4-Benzyl-2-phenyl-2-oxazolin-5-one	5874-61-3	C₁₆H₁₃NO₂	详情	详情
(XV)	49083	N-(1-benzyl-3,3,3-trifluoro-2-oxopropyl)benzamide		C₁₇H₁₄F₃NO₂	详情	详情
(XVI)	49084	N-(1-benzyl-3,3,3-trifluoro-2-hydroxypropyl)benzamide		C₁₇H₁₆F₃NO₂	详情	详情
(XVII)	49085	3-amino-1,1,1-trifluoro-4-phenyl-2-butanol		C₁₀H₁₂F₃NO	详情	详情
(XVIII)	49086	benzyl 1-[2-[(1-benzyl-3,3,3-trifluoro-2-hydroxypropyl)amino]-2-oxoethyl]-2-(4-fluorophenyl)-6-oxo-1,6-dihydro-5-pyrimidinylcarbamate		C₃₀H₂₆F₄N₄O₅	详情	详情
(XIX)	49087	benzyl 1-[2-[(1-benzyl-3,3,3-trifluoro-2-oxopropyl)amino]-2-oxoethyl]-2-(4-fluorophenyl)-6-oxo-1,6-dihydro-5-pyrimidinylcarbamate		C₃₀H₂₄F₄N₄O₅	详情	详情

Extended Information