3-(1-amino-6-isoquinolinyl)alanine -Drug Synthesis Database

【结构式】

【分子编号】30062

【品名】3-(1-amino-6-isoquinolinyl)alanine

【CA登记号】

【分子式】C₁₂H₁₃N₃O₂

【分子量】231.25424

【元素组成】C 62.33% H 5.67% N 18.17% O 13.84%

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：(XII)

Oxidation of 6-bromoisoquinoline (I) with meta-chloroperbenzoic acid, and subsequent addition of HCl provided the quinoline N-oxide hydrochloride (II). This was treated with POCl3 at 90 C to afford 6-bromo-1-chloroisoquinoline (III). Displacement of the chlorine atom of (III) for potassium phenoxide at 140 C gave phenyl ether (IV), which was subsequently reacted with ammonium acetate at 150 C to produce aminoisoquinoline (V). After protection of (V) as the benzamide (VI) by means of benzoic anhydride and pyridine, lithium-halogen exchange, followed by quenching with DMF furnished aldehyde (VII). Reduction of (VII) with NaBH4 gave alcohol (VIII). This was converted to chloride (IX) by conversion to the corresponding mesylate and further displacement with LiCl. Alkylation of (IX) with the sodium salt of N-Boc diethyl aminomalonate (X) yielded the isoquinolylmethyl malonate (XI). Hydrolysis and decarboxylation of (XI) with HCl in aqueous AcOH generated the amino acid (XII).

参考文献中间体

合成目标

【1】 Jenneboer, A.J.s.M.; van Galen, P.J.M.; van Boeckel, C.A.A.; Rood, A.M.M.; Lucas, H.; Noach, A.B.J.; van Dinther, T.G.; Rewinkel, J.B.M.; 1-Aminoisoquinoline as benzamidine isostere in the design and synthesis of orally active thrombin inhibitors. Bioorg Med Chem Lett 1999, 9, 5, 685.
【2】 Van Galen, P.J.M.; Rewinkel, J.B.M.; Van Boeckel, C.A.A. (Akzo Nobel N.V.); Heterocyclic derivs. and their use as antithrombotic agents. EP 0975600; WO 9847876 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(VIII	30058	N-[6-(hydroxymethyl)-1-isoquinolinyl]benzamide		C₁₇H₁₄N₂O₂	详情	详情
(I)	30051	6-bromoisoquinoline		C₉H₆BrN	详情	详情
(II)	30052	6-bromo-2-hydroxyisoquinolinium chloride		C₉H₇BrClNO	详情	详情
(III)	30053	6-bromo-1-chloroisoquinoline		C₉H₅BrClN	详情	详情
(IV)	30054	6-bromo-1-isoquinolinyl phenyl ether; 6-bromo-1-phenoxyisoquinoline		C₁₅H₁₀BrNO	详情	详情
(V)	30055	6-bromo-1-isoquinolinamine; 6-bromo-1-isoquinolinylamine		C₉H₇BrN₂	详情	详情
(VI)	30056	N-(6-bromo-1-isoquinolinyl)benzamide		C₁₆H₁₁BrN₂O	详情	详情
(VII)	30057	N-(6-formyl-1-isoquinolinyl)benzamide		C₁₇H₁₂N₂O₂	详情	详情
(IX)	20059	4-azidobenzoic acid	6427-66-3	C₇H₅N₃O₂	详情	详情
(X)	30060	diethyl 2-[(tert-butoxycarbonyl)amino]malonate		C₁₂H₂₁NO₆	详情	详情
(XI)	30061	diethyl 2-[[1-(benzoylamino)-6-isoquinolinyl]methyl]-2-[(tert-butoxycarbonyl)amino]malonate		C₂₉H₃₃N₃O₇	详情	详情
(XII)	30062	3-(1-amino-6-isoquinolinyl)alanine		C₁₂H₁₃N₃O₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XII)

Compound (XII) was protected as the tert-butyl carbamate (XIII) with Boc2O, and then coupled with piperidine using TBTU to give amide (XIV). The condensation of sulfonyl chloride (XVI) with L-aspartic mono tert-butyl ester (XVII) gave the N-sulfonylaspartate (XVIII). This was finally coupled with aminoamide (XV) by means of DCC and HOBt to yield the title compound.

参考文献中间体

合成目标

【1】 Jenneboer, A.J.s.M.; van Galen, P.J.M.; van Boeckel, C.A.A.; Rood, A.M.M.; Lucas, H.; Noach, A.B.J.; van Dinther, T.G.; Rewinkel, J.B.M.; 1-Aminoisoquinoline as benzamidine isostere in the design and synthesis of orally active thrombin inhibitors. Bioorg Med Chem Lett 1999, 9, 5, 685.
【2】 Van Galen, P.J.M.; Rewinkel, J.B.M.; Van Boeckel, C.A.A. (Akzo Nobel N.V.); Heterocyclic derivs. and their use as antithrombotic agents. EP 0975600; WO 9847876 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(XII)	30062	3-(1-amino-6-isoquinolinyl)alanine		C₁₂H₁₃N₃O₂	详情	详情
(XIII)	30063	3-(1-amino-6-isoquinolinyl)-N-(tert-butoxycarbonyl)alanine		C₁₇H₂₁N₃O₄	详情	详情
(XIV)	30064	tert-butyl 1-[(1-amino-6-isoquinolinyl)methyl]-2-oxo-2-(1-piperidinyl)ethylcarbamate		C₂₂H₃₀N₄O₃	详情	详情
(XV)	30065	2-amino-3-(1-amino-6-isoquinolinyl)-1-(1-piperidinyl)-1-propanone		C₁₇H₂₂N₄O	详情	详情
(XVI)	30066	4-Methoxy-2,3,6-trimethylbenzenesulfonyl chloride	80745-07-9	C₁₀H₁₃ClO₃S	详情	详情
(XVII)	26564	(2S)-2-amino-4-(tert-butoxy)-4-oxobutyric acid	3057-74-7	C₈H₁₅NO₄	详情	详情
(XVIII)	30067	(2S)-4-(tert-butoxy)-2-[[(4-methoxy-2,3,6-trimethylphenyl)sulfonyl]amino]-4-oxobutyric acid		C₁₈H₂₇NO₇S	详情	详情

Extended Information