N-(Tert-butoxycarbonyl)-DL-phenylalanine isobutoxycarbonyl anhydride -Drug Synthesis Database

【结构式】

【分子编号】21836

【品名】N-(Tert-butoxycarbonyl)-DL-phenylalanine isobutoxycarbonyl anhydride

【CA登记号】

【分子式】C₁₉H₂₇NO₆

【分子量】365.42652

【元素组成】C 62.45% H 7.45% N 3.83% O 26.27%

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：(II)

N-Boc-Phenylalanine (I) was treated with isobutyl chloroformate and N-methylmorpholine, and the resulting mixed anhydride (II) was coupled to 2-aminobenzophenone (III) to yield the corresponding amide (IV). After Boc deprotection of (IV) with HCl in EtOAc, the intermediate aminoketone was cyclized with NaOH to the benzodiazepine (V). Alkylation of (V) with 3-nitrobenzyl bromide (VI) in the presence of t-BuOK in THF gave the (nitrobenzyl)benzodiazepine (VII). The nitro group of (VV) was subsequently reduced with SnCl2 in boiling EtOAc to affford (VIII). Then, the resulting amine (VIII) was treated with N,N'-di-Boc-thiourea (IX) in the presence of HgCl2 to provide the diprotected guanidine (X), which was finally deprotected with trifluoroacetic acid in CH2Cl2.

参考文献中间体

合成目标

【1】 Dziadulewicz, E.K.; et al.; The design of non-peptide human bradykinin B2 receptor antagonists employing the benzodiazepine peptidomimetic scaffold. Bioorg Med Chem Lett 1999, 9, 3, 463.

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)	21835	N-(tert-butoxycarbonyl)phenylalanine	4530-18-1	C₁₄H₁₉NO₄	详情	详情
(II)	21836	N-(Tert-butoxycarbonyl)-DL-phenylalanine isobutoxycarbonyl anhydride		C₁₉H₂₇NO₆	详情	详情
(IV)	21838	tert-butyl 2-(2-benzoylanilino)-1-benzyl-2-oxoethylcarbamate		C₂₇H₂₈N₂O₄	详情	详情
(V)	21839	3-benzyl-5-phenyl-1,3-dihydro-2H-1,4-benzodiazepin-2-one		C₂₂H₁₈N₂O	详情	详情
(VI)	19636	1-(bromomethyl)-3-nitrobenzene	3958-57-4	C₇H₆BrNO₂	详情	详情
(VII)	21841	3-benzyl-1-(3-nitrobenzyl)-5-phenyl-1,3-dihydro-2H-1,4-benzodiazepin-2-one		C₂₉H₂₃N₃O₃	详情	详情
(VIII)	21842	1-(3-aminobenzyl)-3-benzyl-5-phenyl-1,3-dihydro-2H-1,4-benzodiazepin-2-one		C₂₉H₂₅N₃O	详情	详情
(IX)	21843	tert-butyl [(tert-butoxycarbonyl)amino]carbothioylcarbamate	145013-05-4	C₁₁H₂₀N₂O₄S	详情	详情
(X)	21844	tert-butyl (Z)-[3-[(3-benzyl-2-oxo-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-1-yl)methyl]anilino][(tert-butoxycarbonyl)amino]methylidenecarbamate		C₄₀H₄₃N₅O₅	详情	详情

合成路线2

该中间体在本合成路线中的序号：(II)

N-Boc-Phenylalanine (I) was treated with isobutyl chloroformate and N-methylmorpholine, and the resulting mixed anhydride (II) was coupled to 2-aminobenzophenone (III) to yield the corresponding amide (IV). After Boc deprotection of (IV) with HCl in EtOAc, the intermediate aminoketone was cyclized with NaOH to the benzodiazepine (V). This was coupled to p-iodonitrobenzene (VI) in the presence of copper and NaOAc in DMF at 150 C to give the (nitrophenyl)benzodiazepine (VII). The nitro group of (VII) was subsequently reduced with SnCl2 in boiling EtOAc to yield (VIII). Then, the resulting amine (VIII) was treated with N,N'-di-Boc-thiourea (IX) in the presence of HgCl2 to provide the diprotected guanidine (X), which was finally deprotected with trifluoroacetic acid in CH2Cl2.

参考文献中间体

合成目标

【1】 Dziadulewicz, E.K.; et al.; The design of non-peptide human bradykinin B2 receptor antagonists employing the benzodiazepine peptidomimetic scaffold. Bioorg Med Chem Lett 1999, 9, 3, 463.

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)	21835	N-(tert-butoxycarbonyl)phenylalanine	4530-18-1	C₁₄H₁₉NO₄	详情	详情
(II)	21836	N-(Tert-butoxycarbonyl)-DL-phenylalanine isobutoxycarbonyl anhydride		C₁₉H₂₇NO₆	详情	详情
(IV)	21838	tert-butyl 2-(2-benzoylanilino)-1-benzyl-2-oxoethylcarbamate		C₂₇H₂₈N₂O₄	详情	详情
(V)	21839	3-benzyl-5-phenyl-1,3-dihydro-2H-1,4-benzodiazepin-2-one		C₂₂H₁₈N₂O	详情	详情
(VI)	21845	1-iodo-4-nitrobenzene	636-98-6	C₆H₄INO₂	详情	详情
(VII)	21846	3-benzyl-1-(4-nitrophenyl)-5-phenyl-1,3-dihydro-2H-1,4-benzodiazepin-2-one		C₂₈H₂₁N₃O₃	详情	详情
(VIII)	21847	1-(4-aminophenyl)-3-benzyl-5-phenyl-1,3-dihydro-2H-1,4-benzodiazepin-2-one		C₂₈H₂₃N₃O	详情	详情
(X)	21848	tert-butyl (Z)-[4-(3-benzyl-2-oxo-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-1-yl)anilino][(tert-butoxycarbonyl)amino]methylidenecarbamate		C₃₉H₄₁N₅O₅	详情	详情

Extended Information