tert-butyl (1S)-1-(5-methyl-4-oxo-4H-thieno[2,3-d][1,3]oxazin-2-yl)ethylcarbamate -Drug Synthesis Database

【结构式】

【分子编号】28659

【品名】tert-butyl (1S)-1-(5-methyl-4-oxo-4H-thieno[2,3-d][1,3]oxazin-2-yl)ethylcarbamate

【CA登记号】

【分子式】C₁₄H₁₈N₂O₄S

【分子量】310.374

【元素组成】C 54.18% H 5.85% N 9.03% O 20.62% S 10.33%

与该中间体有关的原料药合成路线共 3 条

合成路线1 合成路线2 合成路线3

合成路线1

该中间体在本合成路线中的序号：(III)

The coupling of 2-amino-4-methylthiophene-3-carboxylic acid ethyl ester (I) with N-(tert-butoxycarbonyl)-L-alanine (II) by means of isobutyl chloroformate and NMM, followed by cyclization with triphenylphosphine in CCl4 gives the thieno-oxazinone (III), which is deprotected with TFA yielding (IV) with a free amino group that is acylated with cinnamic acid by means of DEC and DIEA.

参考文献中间体

合成目标

【1】 Tew, D.G.; Pinto, I.L.S.M.; Jarvest, R.L.; Jennings, L.J.; Dabrowski, C.E.; Fernandez, A.V.; Lavery, P.; Inhibition of herpes proteases and antiviral activity of 2-substituted thieno[2,3-d]oxazinones. Bioorg Med Chem Lett 1999, 9, 3, 443.
【2】 Jarvest, R.L.; Jennings, L.J.A.; Pinto, I.L. (SmithKline Beecham plc); Thienoxazinone derivs. useful as antiviral agents. WO 9727200 .

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)	29512	ethyl 2-amino-4-methyl-3-thiophenecarboxylate	43088-42-2	C₈H₁₁NO₂S	详情	详情
(II)	26450	Boc-L-Alanine;(S)-2-((tert-butoxycarbonyl)amino)propanoic acid;N-Boc-L-alanine; (2S)-2-[(tert-butoxycarbonyl)amino]propionic acid	15761-38-3	C₈H₁₅NO₄	详情	详情
(III)	28659	tert-butyl (1S)-1-(5-methyl-4-oxo-4H-thieno[2,3-d][1,3]oxazin-2-yl)ethylcarbamate		C₁₄H₁₈N₂O₄S	详情	详情
(IV)	28660	2-[(1S)-1-aminoethyl]-5-methyl-4H-thieno[2,3-d][1,3]oxazin-4-one		C₉H₁₀N₂O₂S	详情	详情
(V)	10449	(Z)-3-Phenyl-2-propenoic acid	621-82-9	C₉H₈O₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(III)

参考文献中间体

合成目标

【1】 Tew, D.G.; Pinto, I.L.S.M.; Jarvest, R.L.; Jennings, L.J.; Dabrowski, C.E.; Fernandez, A.V.; Lavery, P.; Inhibition of herpes proteases and antiviral activity of 2-substituted thieno[2,3-d]oxazinones. Bioorg Med Chem Lett 1999, 9, 3, 443.
【2】 Jarvest, R.L.; Jennings, L.J.A.; Pinto, I.L. (SmithKline Beecham plc); Thienoxazinone derivs. useful as antiviral agents. WO 9727200 .

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)	29512	ethyl 2-amino-4-methyl-3-thiophenecarboxylate	43088-42-2	C₈H₁₁NO₂S	详情	详情
(II)	26450	Boc-L-Alanine;(S)-2-((tert-butoxycarbonyl)amino)propanoic acid;N-Boc-L-alanine; (2S)-2-[(tert-butoxycarbonyl)amino]propionic acid	15761-38-3	C₈H₁₅NO₄	详情	详情
(III)	28659	tert-butyl (1S)-1-(5-methyl-4-oxo-4H-thieno[2,3-d][1,3]oxazin-2-yl)ethylcarbamate		C₁₄H₁₈N₂O₄S	详情	详情
(IV)	28660	2-[(1S)-1-aminoethyl]-5-methyl-4H-thieno[2,3-d][1,3]oxazin-4-one		C₉H₁₀N₂O₂S	详情	详情
(V)	29513	(E)-3-(5-bromo-2-thienyl)-2-propenoic acid		C₇H₅BrO₂S	详情	详情

合成路线3

该中间体在本合成路线中的序号：(III)

The cyclization of 2-amino-4-methylthiophene-3-carboxylic acid (I) with N-(tert-butoxycarbonyl)-L-alanine (II), by means of 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide (DEC) and HOBT in DMF gives the protected thienooxazinone (III), which is deprotected with trifluoroacetic acid in dichloro methane yielding 2-(1(S)-aminoethyl)-5-methyl-4H-thieno[2,3-d][1,3]oxazin-4-one (IV). Finally, this compound is acylated with 4-oxo-4-phenyl-2(E)-butenoic acid (VI) by means of DEC and diisopropylethylamine in DMF.

参考文献中间体

合成目标

【1】 Jarvest, R.L.; Pinto, I.L.; Clarke, B.; et al.; Inhibition of human cytomegalovirus protease by enedione derivatives of thieno[2,3-d]oxazinones through a novel dual acylation/alkylation mechanism. Bioorg Med Chem Lett 1999, 9, 3, 449.
【2】 Jarvest, R.L.; Jennings, L.J.A.; Pinto, I.L. (SmithKline Beecham plc); Thienoxazinone derivs. useful as antiviral agents. WO 9727200 .

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)	28658	2-amino-4-methyl-3-thiophenecarboxylic acid		C₆H₇NO₂S	详情	详情
(II)	26450	Boc-L-Alanine;(S)-2-((tert-butoxycarbonyl)amino)propanoic acid;N-Boc-L-alanine; (2S)-2-[(tert-butoxycarbonyl)amino]propionic acid	15761-38-3	C₈H₁₅NO₄	详情	详情
(III)	28659	tert-butyl (1S)-1-(5-methyl-4-oxo-4H-thieno[2,3-d][1,3]oxazin-2-yl)ethylcarbamate		C₁₄H₁₈N₂O₄S	详情	详情
(IV)	28660	2-[(1S)-1-aminoethyl]-5-methyl-4H-thieno[2,3-d][1,3]oxazin-4-one		C₉H₁₀N₂O₂S	详情	详情
(V)	28661	(E)-4-oxo-4-phenyl-2-butenoic acid	583-06-2	C₁₀H₈O₃	详情	详情

Extended Information