(2S)-2-amino-N,N-bis(2-thienylmethyl)hexanamide -Drug Synthesis Database

【结构式】

【分子编号】38468

【品名】(2S)-2-amino-N,N-bis(2-thienylmethyl)hexanamide

【CA登记号】

【分子式】C₁₆H₂₂N₂OS₂

【分子量】322.49556

【元素组成】C 59.59% H 6.88% N 8.69% O 4.96% S 19.89%

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)

Reductive condensation of 2-thienylmethylamine (I) with 2-thiophenecarboxaldehyde (II) in the presence of NaBH(OAc)3 provided bis(2-thienylmethyl)amine (III), which was coupled with N-Boc-2-aminohexanoic acid (IV) by means of EDC and HOBt, yielding amide (V). Acid deprotection of the Boc group of (V) then gave amine (VI).

参考文献中间体

合成目标

【1】 Scott, I.L.; et al.; Novel N,N-disubstituted amides that are highly potent VLA-4 antagonists. 219th ACS Natl Meet (March 26 2000, San Francisco) 2000, Abst MEDI 284.
【2】 Raju, B.G.; Scott, I.L.; Biediger, R.J.; Market, R.V.; Grabbe, V.O.; Kassir, J.M.; Kogan, T.P.; Lin, S. (Texas Biotechnology Corp.); N,N-Disubstd. amides that inhibit the binding of integrins to their receptors. US 6096773; WO 9952493; WO 9952898 .

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)	33238	2-thienylmethylamine; 2-thienylmethanamine	27757-85-3	C₅H₇NS	详情	详情
(II)	30732	2-thiophenecarbaldehyde; Thiophene-2-carboxaldehyde	98-03-3	C₅H₄OS	详情	详情
(III)	38466	2-thienyl-N-(2-thienylmethyl)methanamine; N,N-bis(2-thienylmethyl)amine		C₁₀H₁₁NS₂	详情	详情
(IV)	20398	(2S)-2-[(tert-butoxycarbonyl)amino]hexanoic acid		C₁₁H₂₁NO₄	详情	详情
(V)	38467	tert-butyl (1S)-1-[[bis(2-thienylmethyl)amino]carbonyl]pentylcarbamate		C₂₁H₃₀N₂O₃S₂	详情	详情
(VI)	38468	(2S)-2-amino-N,N-bis(2-thienylmethyl)hexanamide		C₁₆H₂₂N₂OS₂	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 3,4-(methylenedioxy)cinnamic (VII) with SOCl2 and then with EtOH provided ethyl ester (VIII). Subsequent conjugate addition of the chiral amine (IX) to ester (VIII) in the presence of BuLi gave amino ester (X). Cleavage of benzyl and alpha-methylbenzyl protecting groups of (X) was then achieved by catalytic hydrogenolysis over Pd/C. The resulting primary amine (XI) was acylated with 4-nitrophenyl chloroformate (XII) to produce carbamate (XIII), which was condensed with amine (VI) to generate urea (XIV). Finally, basic hydrolysis of the ethyl ester of (XIV) furnished the title carboxylic acid.

参考文献中间体

合成目标

【1】 Scott, I.L.; et al.; Novel N,N-disubstituted amides that are highly potent VLA-4 antagonists. 219th ACS Natl Meet (March 26 2000, San Francisco) 2000, Abst MEDI 284.
【2】 Raju, B.G.; Scott, I.L.; Biediger, R.J.; Market, R.V.; Grabbe, V.O.; Kassir, J.M.; Kogan, T.P.; Lin, S. (Texas Biotechnology Corp.); N,N-Disubstd. amides that inhibit the binding of integrins to their receptors. US 6096773; WO 9952493; WO 9952898 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(VI)	38468	(2S)-2-amino-N,N-bis(2-thienylmethyl)hexanamide		C₁₆H₂₂N₂OS₂	详情	详情
(VII)	11634	(E)-3-(1,3-Benzodioxol-5-yl)-2-propenoic acid; 3,4-(Methylenedioxy)cinnamic acid	2373-80-0	C₁₀H₈O₄	详情	详情
(VIII)	38469	ethyl (E)-3-(1,3-benzodioxol-5-yl)-2-propenoate		C₁₂H₁₂O₄	详情	详情
(IX)	38470	(1S)-N-benzyl-1-phenyl-1-ethanamine; N-benzyl-N-[(1S)-1-phenylethyl]amine	38235-77-7	C₁₅H₁₇N	详情	详情
(X)	38471	ethyl (3S)-3-(1,3-benzodioxol-5-yl)-3-[benzyl[(1S)-1-phenylethyl]amino]propanoate		C₂₇H₂₉NO₄	详情	详情
(XI)	38472	ethyl (3S)-3-amino-3-(1,3-benzodioxol-5-yl)propanoate		C₁₂H₁₅NO₄	详情	详情
(XII)	16605	4-Nitrophenyl chloroformate; 1-[(Chlorocarbonyl)oxy]-4-nitrobenzene	7693-46-1	C₇H₄ClNO₄	详情	详情
(XIII)	38473	ethyl (3S)-3-(1,3-benzodioxol-5-yl)-3-[[(4-nitrophenoxy)carbonyl]amino]propanoate		C₁₉H₁₈N₂O₈	详情	详情
(XIV)	38474	ethyl (3S)-3-(1,3-benzodioxol-5-yl)-3-([[((1S)-1-[[bis(2-thienylmethyl)amino]carbonyl]pentyl)amino]carbonyl]amino)propanoate		C₂₉H₃₅N₃O₆S₂	详情	详情

Extended Information