tert-butyl 3-aminobenzylcarbamate -Drug Synthesis Database

【结构式】

【分子编号】39660

【品名】tert-butyl 3-aminobenzylcarbamate

【CA登记号】

【分子式】C₁₂H₁₈N₂O₂

【分子量】222.2872

【元素组成】C 64.84% H 8.16% N 12.6% O 14.4%

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：(VII)

The oxidation of 3-methoxy-4-methylnitrobenzene (I) with CrO3, H2SO4 and AC2O in acetic acid gives the gem-diacetate (II), which is hydrolyzed with HCl in refluxing dioxane to yield 2-methoxy-4-nitrobenzaldehyde (III). Cyclization of (III) with tosylmethyl isocyanide and K2CO3 in refluxing methanol affords 3-methoxy-4-(5-oxazolyl)nitrobenzene (IV), which is reduced with H2 over Pd/C in ethyl acetate to provide the corresponding aniline (V). The activation of (V) with carbonyldiimidazole (CDI) in THF gives the carboxamide (VI), which is condensed with 3-(tert-butoxycarbonylaminomethyl)aniline (VII), obtained by reaction of 3-aminobenzylamine with Boc2O, and DMAP in refluxing THF to yield the urea (IX). Deprotection of (IX) with TFA in dichloromethane affords the free benzylamine (X), which is finally condensed with the 3-furyl ester of the succinimidyl-activated carbonate (XI) by means of TEA in dichloromethane/DMF.

参考文献中间体

合成目标

【1】 Martín, L.; Sorbera, L.A.; Castañer, J.; Silvestre, J.S.; VX-497. Drugs Fut 2000, 25, 8, 809.
【2】 Armistead, D.M.; Badia, M.C.; Bemis, G.W.; Bethiel, R.S.; Frank, C.A.; Novak, P.M.; Ronkin, S.M.; Saunders, J.O. (Vertex Pharmaceuticals Inc.); Urea derivs. as inhibitors of IMPDH enzyme. EP 0902782; US 5807876; US 6054472; WO 9740028 .

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)	39654	methyl 2-methyl-5-nitrophenyl ether; 2-methoxy-1-methyl-4-nitrobenzene	13120-77-9	C₈H₉NO₃	详情	详情
(II)	39655	(acetoxy)(2-methoxy-4-nitrophenyl)methyl acetate		C₁₂H₁₃NO₇	详情	详情
(III)	39656	2-methoxy-4-nitrobenzaldehyde		C₈H₇NO₄	详情	详情
(IV)	39657	methyl 5-nitro-2-(1,3-oxazol-5-yl)phenyl ether; 5-(2-methoxy-4-nitrophenyl)-1,3-oxazole		C₁₀H₈N₂O₄	详情	详情
(V)	39658			C₁₀H₁₀N₂O₂	详情	详情
(VI)	39659	N-[3-methoxy-4-(1,3-oxazol-5-yl)phenyl]-1H-imidazole-1-carboxamide		C₁₄H₁₂N₄O₃	详情	详情
(VII)	39660	tert-butyl 3-aminobenzylcarbamate		C₁₂H₁₈N₂O₂	详情	详情
(VIII)	39661	3-(aminomethyl)aniline; 3-aminobenzylamine	4403-70-7	C₇H₁₀N₂	详情	详情
(IX)	39662	tert-butyl 3-([[3-methoxy-4-(1,3-oxazol-5-yl)anilino]carbonyl]amino)benzylcarbamate		C₂₃H₂₆N₄O₅	详情	详情
(X)	39663	N-[3-(aminomethyl)phenyl]-N'-[3-methoxy-4-(1,3-oxazol-5-yl)phenyl]urea		C₁₈H₁₈N₄O₃	详情	详情
(XI)	39664	1-([[(3S)tetrahydro-3-furanyloxy]carbonyl]oxy)-2,5-pyrrolidinedione		C₉H₁₁NO₆	详情	详情

合成路线2

该中间体在本合成路线中的序号：(II)

Reduction of N-Boc-3-nitrobenzylamine (I) by catalytic hydrogenation over Pd/C yields aniline (II). This is then condensed with S-methyl-2-thiophenethiocarboximide (III) to furnish amidine (IV). Subsequent acidic Boc group cleavage yields amine (V).

参考文献中间体

合成目标

【1】 Auvin, S.; Auget, M.; Navet, E.; Harnett, J.J.; Viossat, I.; Schulz, J.; Bigg, D.; Chabrier, P.-E.; Novel inhibitors of neuronal nitric oxide synthase with potent antioxidant properties. Bioorg Med Chem Lett 2003, 13, 2, 209.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	63368	1,1-dimethylethyl (3-nitrophenyl)methylcarbamate	C₁₂H₁₆N₂O₄	详情	详情
(II)	39660	tert-butyl 3-aminobenzylcarbamate	C₁₂H₁₈N₂O₂	详情	详情
(III)	34836	methyl 2-thiophenecarbimidothioate	C₆H₇NS₂	详情	详情
(IV)	63369	1,1-dimethylethyl (3-{[imino(2-thiophenyl)methyl]amino}phenyl)methylcarbamate	C₁₇H₂₁N₃O₂S	详情	详情
(V)	63370	N-[3-(aminomethyl)phenyl]-2-thiophenecarboximidamide	C₁₂H₁₃N₃S	详情	详情

Extended Information