2-methylacrylic acid -Drug Synthesis Database

【结构式】

【分子编号】33550

【品名】2-methylacrylic acid

【CA登记号】79-41-4

【分子式】C₄H₆O₂

【分子量】86.09044

【元素组成】C 55.81% H 7.02% O 37.17%

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：(X)

It is prepared by hydrolysis with ammonia in methanol of N-(3-acetylthio-2-methylpropanoyl)-L-proline (I). Compound (I) can be obtained in three different ways: 1) The reaction of L-proline tert-butyl ester (II) with 3-acetylthio-2-methyl-propanoic acid (III) by means of dicyclohexylcarbodiimide in CH2Cl2 gives N-(3-acetylthio-2-methylpropanoyl)-L-proline tert-butyl ester (IV), which is hydrolyzed with trifluoroacetic acid in anisole. 2) By condensation of L-proline (V) with 3-acetylthio-2-methylpropanoyl chloride (VI) (prepared from the corresponding acid (III) with SOCl2) by means of NaOH in water. 3) The condensation of L-proline (V) with methacryloyl chloride (VII) by means of NaHCO3 in water yields N-methacryloyl-L-proline (VIII), which is then treated with thiolacetic acid (A) and azobisisobutyronitrile. The acid (III) is obtained by addition of thiolacetic acid (IX) to methacrylic acid (X) at 100 C.

参考文献中间体

合成目标

【1】 Cushman, D.W.; Ondetti, M.A.; Azetidine-2-carboxylic acid derivatives. BE 0851361; DD 283999; JP 58189113; JP 58189158; US 4046889; US 4154840 .
【2】 Roberts, P.J.; Castaner, J.; Captopril. Drugs Fut 1978, 3, 11, 795.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(A)	33555	Thiolacetic acid; Thioacetic acid; ethanethioic O-acid; Ethanethioic acid	507-09-5	C₂H₄OS	详情	详情
(I)	33552	(2S)-1-[(2S)-3-(acetylsulfanyl)-2-methylpropanoyl]-2-pyrrolidinecarboxylic acid	65167-28-4	C₁₁H₁₇NO₄S	详情	详情
(II)	19832	tert-butyl (2S)-2-pyrrolidinecarboxylate		C₉H₁₇NO₂	详情	详情
(III)	33556	3-(acetylsulfanyl)-2-methylpropionic acid		C₆H₁₀O₃S	详情	详情
(IV)	33551	tert-butyl (2S)-1-[(2S)-3-(acetylsulfanyl)-2-methylpropanoyl]-2-pyrrolidinecarboxylate		C₁₅H₂₅NO₄S	详情	详情
(V)	16731	L-proline	147-85-3	C₅H₉NO₂	详情	详情
(VI)	33557	S-(3-chloro-2-methyl-3-oxopropyl) ethanethioate		C₆H₉ClO₂S	详情	详情
(VII)	33553	2-methylacryloyl chloride	920-46-7	C₄H₅ClO	详情	详情
(VIII)	33554	(2S)-1-methacryloyl-2-pyrrolidinecarboxylic acid		C₉H₁₃NO₃	详情	详情
(IX)	12893	Ethanethioic S-acid		C₂H₄OS	详情	详情
(X)	33550	2-methylacrylic acid	79-41-4	C₄H₆O₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

参考文献中间体

合成目标

【1】 Zepp CM.Method for preparation captopril and its analogues:WO,Patent 9,002,732,1990.

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)	33550	2-methylacrylic acid	79-41-4	C₄H₆O₂	详情	详情
(II)	11376	Pyrrolidine	123-75-1	C₄H₉N	详情	详情
(III)	16731	L-proline	147-85-3	C₅H₉NO₂	详情	详情
(IV)	69593	(S)-1-((S)-2-methyl-3-((pyrrolidine-1-carbonothioyl)thio)propanoyl)pyrrolidine-2-carboxylic acid		C₁₄H₂₂N₂O₃S₂	详情	详情

合成路线3

该中间体在本合成路线中的序号：(II)

参考文献中间体

合成目标

【1】 Onedetti MA.Pyrrolo or pyrido[2,1-c][1,4] thiazines or thizapines:US,Patent 2,225,495,1980.
【2】 Snatzke G,Decorte E,Kovac T,et al.Attempted diastereoselective preparation chiroptical properties of (2S)-1-(3-mercapto-2-methyl-1-oxo-propyl)-L-proline(captopril) and some congeners.Croat Chem Acta,1989,62:325.
【3】 Evers MC.Captopril preparation by cyclisation and dehydration of N-2(S)-3-hydroxy 2-methyl-propionyl-S-thioproline and reaction of product with an aq or alcoholic base:NL,Patent 8,303,983,1985.

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)	69594	(S)-1-(tert-butoxycarbonyl)pyrrolidine-2-carbothioic S-acid		C₁₀H₁₇NO₃S	详情	详情
(II)	33550	2-methylacrylic acid	79-41-4	C₄H₆O₂	详情	详情
(III)	69595	3-(((S)-1-(tert-butoxycarbonyl)pyrrolidine-2-carbonyl)thio)-2-methylpropanoic acid		C₁₄H₂₃NO₅S	详情	详情
(IV)	69596	4-methylhexahydropyrrolo[2,1-c][1,4]thiazepine-1,5-dione		C₉H₁₃NO₂S	详情	详情

Extended Information