(4R)-5,5-dimethyl-N-(2-methylbenzyl)-1,3-thiazolidine-4-carboxamide -Drug Synthesis Database

【结构式】

【分子编号】34780

【品名】(4R)-5,5-dimethyl-N-(2-methylbenzyl)-1,3-thiazolidine-4-carboxamide

【CA登记号】

【分子式】C₁₄H₂₀N₂OS

【分子量】264.39168

【元素组成】C 63.6% H 7.62% N 10.6% O 6.05% S 12.13%

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：(VI)

Treatment of penicillamine (I) with formaldehyde produced thiazolidine (II), which was then protected with Boc2O to give carbamate (III). Coupling of (III) with 2-methylbenzylamine (IV) by means of either diphenylphosphoryl chloride (DPPCl), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide-HCl (EDC) or dicyclohexylcarbodiimide (DCC) afforded the corresponding amide (V). After acid cleavage of the Boc group of (V), the deprotected thiazolidine (VI) was coupled with N-Boc-(S,S)-3-amino-2-hydroxy-4-phenylbutyric acid (VII) using EDC to give diamide (VIII). Further acid deprotection of the Boc group of (VIII) yielded (IX). This was finally coupled with 3-hydroxy-2-methylbenzoic acid (X) to furnish the title compound. Alternatively, amine (IX) was coupled with 3-acetoxy-2-methylbenzoic acid (XI) to afford (XII), which was then deacetylated using NaOH in MeOH.

参考文献中间体

合成目标

【1】 Mimoto, T.; Takaku, H.; Kato, R.; et al.; Structure-activity relationship of small-sized HIV protease inhibitors containing allophenylnorstatine. J Med Chem 1999, 42, 10, 1789.
【2】 Kiso, Y.; Design and synthesis of a covalently linked HIV-1 protease dimer analog and peptidomimetic inhibitors. Yuki Gosei Kagaku Kyokaishi 1998, 56, 11, 896.
【3】 Kato, R.; Mimoto, T.; Fukazawa, T.; Morohashi, N.; Kiso, Y. (Japan Energy Corp.); HIV-protease inhibitors. CA 2179935; EP 0751145; JP 1998025242 .

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)	12567	(2S)-2-Amino-3-methyl-3-sulfanylbutyric acid; Penicillamine; 3-Mercapto-L-valine	1113-41-3	C₅H₁₁NO₂S	详情	详情
(II)	34776	(4R)-5,5-dimethyl-1,3-thiazolidine-4-carboxylic acid	72778-00-8	C₆H₁₁NO₂S	详情	详情
(III)	34777	(4R)-3-(tert-butoxycarbonyl)-5,5-dimethyl-1,3-thiazolidine-4-carboxylic acid		C₁₁H₁₉NO₄S	详情	详情
(IV)	34778	(2-methylphenyl)methanamine; 2-methylbenzylamine	89-93-0	C₈H₁₁N	详情	详情
(V)	34779	tert-butyl (4R)-5,5-dimethyl-4-[[(2-methylbenzyl)amino]carbonyl]-1,3-thiazolidine-3-carboxylate		C₁₉H₂₈N₂O₃S	详情	详情
(VI)	34780	(4R)-5,5-dimethyl-N-(2-methylbenzyl)-1,3-thiazolidine-4-carboxamide		C₁₄H₂₀N₂OS	详情	详情
(VII)	34781	(2S,3S)-3-[(tert-butoxycarbonyl)amino]-2-methyl-4-phenylbutyric acid		C₁₆H₂₃NO₄	详情	详情
(VIII)	34782	tert-butyl (1S,2S)-1-benzyl-3-((4R)-5,5-dimethyl-4-[[(2-methylbenzyl)amino]carbonyl]-1,3-thiazolidin-3-yl)-2-methyl-3-oxopropylcarbamate		C₃₀H₄₁N₃O₄S	详情	详情
(IX)	34783	(4R)-3-[(2S,3S)-3-amino-2-methyl-4-phenylbutanoyl]-5,5-dimethyl-N-(2-methylbenzyl)-1,3-thiazolidine-4-carboxamide		C₂₅H₃₃N₃O₂S	详情	详情
(X)	16759	3-hydroxy-2-methylbenzoic acid	603-80-5	C₈H₈O₃	详情	详情
(XI)	34784	3-(acetoxy)-2-methylbenzoic acid	168899-58-9	C₁₀H₁₀O₄	详情	详情
(XII)	34785	3-([[(1S,2S)-1-benzyl-3-((4R)-5,5-dimethyl-4-[[(2-methylbenzyl)amino]carbonyl]-1,3-thiazolidin-3-yl)-2-methyl-3-oxopropyl]amino]carbonyl)-2-methylphenyl acetate		C₃₅H₄₁N₃O₅S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VI)

Treatment of penicillamine (I) with formaldehyde produced thiazolidine (II), which was then protected with Boc2O to give carbamate (III). Coupling of (III) with 2-methylbenzylamine (IV) by means of either diphenylphosphoryl chloride (DPP-Cl) or 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide-HCl (EDC) afforded the corresponding amide (V). After acid cleavage of the Boc group of (V), the deprotected thiazolidine (VI) was coupled with N-Boc-(S,S)-3-amino-2-hydroxy-4-phenylbutyric acid (VII) using EDC to give diamide (VIII). Further acid deprotection of the Boc group of (VIII) yielded (IX). This was finally coupled with 2-ethyl-3-hydroxybenzoic acid (X) to furnish the title compound. Alternatively, amine (IX) was coupled with 3-acetoxy-2-ethylbenzoic acid (XI) to afford (XII), which was then deacetylated using NaOH in MeOH.

参考文献中间体

合成目标

【1】 Kiso, Y.; Design and synthesis of a covalently linked HIV-1 protease dimer analog and peptidomimetic inhibitors. Yuki Gosei Kagaku Kyokaishi 1998, 56, 11, 896.
【2】 Mimoto, T.; Takaku, H.; Kato, R.; et al.; Structure-activity relationship of small-sized HIV protease inhibitors containing allophenylnorstatine. J Med Chem 1999, 42, 10, 1789.
【3】 Kato, R.; Mimoto, T.; Fukazawa, T.; Morohashi, N.; Kiso, Y. (Japan Energy Corp.); HIV-protease inhibitors. CA 2179935; EP 0751145; JP 1998025242 .

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)	12567	(2S)-2-Amino-3-methyl-3-sulfanylbutyric acid; Penicillamine; 3-Mercapto-L-valine	1113-41-3	C₅H₁₁NO₂S	详情	详情
(II)	34776	(4R)-5,5-dimethyl-1,3-thiazolidine-4-carboxylic acid	72778-00-8	C₆H₁₁NO₂S	详情	详情
(III)	34777	(4R)-3-(tert-butoxycarbonyl)-5,5-dimethyl-1,3-thiazolidine-4-carboxylic acid		C₁₁H₁₉NO₄S	详情	详情
(IV)	34778	(2-methylphenyl)methanamine; 2-methylbenzylamine	89-93-0	C₈H₁₁N	详情	详情
(V)	34779	tert-butyl (4R)-5,5-dimethyl-4-[[(2-methylbenzyl)amino]carbonyl]-1,3-thiazolidine-3-carboxylate		C₁₉H₂₈N₂O₃S	详情	详情
(VI)	34780	(4R)-5,5-dimethyl-N-(2-methylbenzyl)-1,3-thiazolidine-4-carboxamide		C₁₄H₂₀N₂OS	详情	详情
(VII)	34781	(2S,3S)-3-[(tert-butoxycarbonyl)amino]-2-methyl-4-phenylbutyric acid		C₁₆H₂₃NO₄	详情	详情
(VIII)	34782	tert-butyl (1S,2S)-1-benzyl-3-((4R)-5,5-dimethyl-4-[[(2-methylbenzyl)amino]carbonyl]-1,3-thiazolidin-3-yl)-2-methyl-3-oxopropylcarbamate		C₃₀H₄₁N₃O₄S	详情	详情
(IX)	34783	(4R)-3-[(2S,3S)-3-amino-2-methyl-4-phenylbutanoyl]-5,5-dimethyl-N-(2-methylbenzyl)-1,3-thiazolidine-4-carboxamide		C₂₅H₃₃N₃O₂S	详情	详情
(X)	34786	2-ethyl-3-hydroxybenzoic acid		C₉H₁₀O₃	详情	详情
(XI)	34787	3-(acetoxy)-2-ethylbenzoic acid		C₁₁H₁₂O₄	详情	详情
(XII)	34788	3-([[(1S,2S)-1-benzyl-3-((4R)-5,5-dimethyl-4-[[(2-methylbenzyl)amino]carbonyl]-1,3-thiazolidin-3-yl)-2-methyl-3-oxopropyl]amino]carbonyl)-2-ethylphenyl acetate		C₃₆H₄₃N₃O₅S	详情	详情

Extended Information