2-[4-(3-methyl-2-thienyl)phenyl]propanal -Drug Synthesis Database

【结构式】

【分子编号】62692

【品名】2-[4-(3-methyl-2-thienyl)phenyl]propanal

【CA登记号】

【分子式】C₁₄H₁₄OS

【分子量】230.33056

【元素组成】C 73.01% H 6.13% O 6.95% S 13.92%

与该中间体有关的原料药合成路线共 4 条

合成路线1 合成路线2 合成路线3 合成路线4

合成路线1

该中间体在本合成路线中的序号：(XVII)

Preparation of the racemic arylpropionic acid (IX) has been reported through a number of different procedures. 4-Aminoacetophenone (XI) was diazotized to (XII) employing isoamyl nitrite and either acetic or fluoboric acid. Then, the Gomberg-Bachmann coupling of diazonium salt (XII) with 3-methylthiophene (XIII) furnished 4-(3-methyl-2-thienyl)acetophenone (XIV). Subsequent Darzen's condensation of acetophenone (XIV) with methyl chloroacetate (II) afforded the glycidic ester (XV), which was further hydrolyzed to acid (XVI), and then decarboxylated to aldehyde (XVII). Oxidation of (XVII) to the key carboxylic acid was performed by treatment with potassium permanganate

参考文献中间体

合成目标

【2】 Arai, H.; Tanaka, K.; Watanabe, I.; Kodama, T.; Hirano, H.; Abe, N.; Nakabayashi, M. (Toyama Chemical Co., Ltd.); Novel 2-[4-(3-methyl-2-thienyl)phenyl]propionic acid and pharmaceutically acceptable salt thereof and method for treating symptoms of inflammation and pain. US 4230719 .
【1】 Kodama, T.; Nakabayashi, M.; Watanabe, I.; Hirano, Y.; Abe, N.; Tanaka, K.; Arai, H. (Toyama Chemical Co., Ltd.); 2-[4-(3-Methyl-2-thienyl)phenyl]propionic acid derivs. and its non-toxic salts. DE 2850485; JP 1981049376 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(II)	10257	methyl 2-chloroacetate; methyl chloroacetate	96-34-4	C₃H₅ClO₂	详情	详情
(IX)	62687	2-[4-(3-methyl-2-thienyl)phenyl]propanoic acid		C₁₄H₁₄O₂S	详情	详情
(XI)	27847	1-(4-aminophenyl)-1-ethanone	99-92-3	C₈H₉NO	详情	详情
(XII)	62688	4-acetylbenzenediazonium		C₈H₇N₂O	详情	详情
(XIII)	12442	3-Methylthiophene	616-44-4	C₅H₆S	详情	详情
(XIV)	62689	1-[4-(3-methyl-2-thienyl)phenyl]-1-ethanone		C₁₃H₁₂OS	详情	详情
(XV)	62690	methyl 3-methyl-3-[4-(3-methyl-2-thienyl)phenyl]-2-oxiranecarboxylate		C₁₆H₁₆O₃S	详情	详情
(XVI)	62691	3-methyl-3-[4-(3-methyl-2-thienyl)phenyl]-2-oxiranecarboxylic acid		C₁₅H₁₄O₃S	详情	详情
(XVII)	62692	2-[4-(3-methyl-2-thienyl)phenyl]propanal		C₁₄H₁₄OS	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XVII)

Acetophenone (XIV) was converted to oxirane (XXI) by treatment with the in situ-generated dimethylsulfonium methylide. Rearrangement of epoxide (XVII) in the presence of molecular sieves furnished aldehyde (XVII), which was converted to acid (IX) by oxidation with sodium chlorite.

参考文献中间体

合成目标

【2】 Arai, H.; Tanaka, K.; Watanabe, I.; Kodama, T.; Hirano, H.; Abe, N.; Nakabayashi, M. (Toyama Chemical Co., Ltd.); Novel 2-[4-(3-methyl-2-thienyl)phenyl]propionic acid and pharmaceutically acceptable salt thereof and method for treating symptoms of inflammation and pain. US 4230719 .
【1】 Kodama, T.; Nakabayashi, M.; Watanabe, I.; Hirano, Y.; Abe, N.; Tanaka, K.; Arai, H. (Toyama Chemical Co., Ltd.); 2-[4-(3-Methyl-2-thienyl)phenyl]propionic acid derivs. and its non-toxic salts. DE 2850485; JP 1981049376 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(IX)	62687	2-[4-(3-methyl-2-thienyl)phenyl]propanoic acid	C₁₄H₁₄O₂S	详情	详情
(XIV)	62689	1-[4-(3-methyl-2-thienyl)phenyl]-1-ethanone	C₁₃H₁₂OS	详情	详情
(XVII)	62692	2-[4-(3-methyl-2-thienyl)phenyl]propanal	C₁₄H₁₄OS	详情	详情
(XXI)	62695	2-methyl-2-[4-(3-methyl-2-thienyl)phenyl]oxirane	C₁₄H₁₄OS	详情	详情

合成路线3

该中间体在本合成路线中的序号：(XVIII)

In a different approach, the precursor aldehyde (XVII) was obtained by addition of the Grignard reagent prepared from chloromethyl ethyl ether (XXV) to acetophenone (XIV), and then rearrangement of the resultant ethoxy alcohol (XXVI) in refluxing AcOH

参考文献中间体

合成目标

【2】 Arai, H.; Tanaka, K.; Watanabe, I.; Kodama, T.; Hirano, H.; Abe, N.; Nakabayashi, M. (Toyama Chemical Co., Ltd.); Novel 2-[4-(3-methyl-2-thienyl)phenyl]propionic acid and pharmaceutically acceptable salt thereof and method for treating symptoms of inflammation and pain. US 4230719 .
【1】 Kodama, T.; Nakabayashi, M.; Watanabe, I.; Hirano, Y.; Abe, N.; Tanaka, K.; Arai, H. (Toyama Chemical Co., Ltd.); 2-[4-(3-Methyl-2-thienyl)phenyl]propionic acid derivs. and its non-toxic salts. DE 2850485; JP 1981049376 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(XIV)	62689	1-[4-(3-methyl-2-thienyl)phenyl]-1-ethanone		C₁₃H₁₂OS	详情	详情
(XVIII)	62692	2-[4-(3-methyl-2-thienyl)phenyl]propanal		C₁₄H₁₄OS	详情	详情
(XXV)	13149	1-(Chloromethoxy)ethane; Chloromethyl ethyl ether	3188-13-4	C₃H₇ClO	详情	详情
(XXVI)	62699	1-ethoxy-2-[4-(3-methyl-2-thienyl)phenyl]-2-propanol		C₁₆H₂₀O₂S	详情	详情

合成路线4

该中间体在本合成路线中的序号：(XVII)

2-(4-Iodophenyl)-2-methyloxirane (XLV) was obtained by addition of dimethylsulfonium methylide to 4-iodoacetophenone (I). Rearrangement of epoxide (XLV) in the presence of molecular sieves led to aldehyde (V), which was protected as the dimethyl acetal (XLVI) upon treatment with trimethyl orthoformate. Palladium-catalyzed condensation of the Grignard reagent (VIII) with aryl iodide (XLVI) furnished the biaryl adduct (XLVII). This was subsequently hydrolyzed to the key aldehyde (XVII) employing AcOH

参考文献中间体

合成目标

【2】 Arai, H.; Tanaka, K.; Watanabe, I.; Kodama, T.; Hirano, H.; Abe, N.; Nakabayashi, M. (Toyama Chemical Co., Ltd.); Novel 2-[4-(3-methyl-2-thienyl)phenyl]propionic acid and pharmaceutically acceptable salt thereof and method for treating symptoms of inflammation and pain. US 4230719 .
【1】 Kodama, T.; Nakabayashi, M.; Watanabe, I.; Hirano, Y.; Abe, N.; Tanaka, K.; Arai, H. (Toyama Chemical Co., Ltd.); 2-[4-(3-Methyl-2-thienyl)phenyl]propionic acid derivs. and its non-toxic salts. DE 2850485; JP 1981049376 .

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)	51497	4'-Iodoacetophenone; 4-Iodoacetophenone; 1-(4-Iodophenyl)ethanone	13329-40-3	C₈H₇IO	详情	详情
(V)	62685	2-(4-iodophenyl)propanal		C₉H₉IO	详情	详情
(VIII)	36973	bromo(3-methyl-2-thienyl)magnesium		C₅H₅BrMgS	详情	详情
(XVII)	62692	2-[4-(3-methyl-2-thienyl)phenyl]propanal		C₁₄H₁₄OS	详情	详情
(XLV)	62715	2-(4-iodophenyl)-2-methyloxirane		C₉H₉IO	详情	详情
(XLVI)	62716	1-(2,2-dimethoxy-1-methylethyl)-4-iodobenzene; 2-(4-iodophenyl)-1-methoxypropyl methyl ether		C₁₁H₁₅IO₂	详情	详情
(XLVII)	62717	1-methoxy-2-[4-(3-methyl-2-thienyl)phenyl]propyl methyl ether; 2-[4-(2,2-dimethoxy-1-methylethyl)phenyl]-3-methylthiophene		C₁₆H₂₀O₂S	详情	详情

Extended Information