1-[4-(3-methyl-2-thienyl)phenyl]-1-ethanone -Drug Synthesis Database

【结构式】

【分子编号】62689

【品名】1-[4-(3-methyl-2-thienyl)phenyl]-1-ethanone

【CA登记号】

【分子式】C₁₃H₁₂OS

【分子量】216.30368

【元素组成】C 72.19% H 5.59% O 7.4% S 14.82%

与该中间体有关的原料药合成路线共 7 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5 合成路线6 合成路线7

合成路线1

该中间体在本合成路线中的序号：(XIV)

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：(XIV)

Alternatively, Darzen's condensation of acetophenone (XIV) with methyl 2-chloropropionate (XVIII) produced glycidic ester (XIX), which was hydrolyzed and decarboxylated to the 3-arylbutanone (XX). The haloform reaction of ketone (XX) with sodium hypobromite generated acid (IX)

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
(XVIII)	35742	methyl (2S)-2-chloropropanoate	C₄H₇ClO₂	详情	详情
(XIX)	62693	methyl 2,3-dimethyl-3-[4-(3-methyl-2-thienyl)phenyl]-2-oxiranecarboxylate	C₁₇H₁₈O₃S	详情	详情
(XX)	62694	3-[4-(3-methyl-2-thienyl)phenyl]-2-butanone	C₁₅H₁₆OS	详情	详情

合成路线3

该中间体在本合成路线中的序号：(XIV)

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4

该中间体在本合成路线中的序号：(XIV)

In an alternative procedure, acetophenone (XIV) was condensed with KCN in the presence of ammonium carbonate to produce hydantoin (XXII). Basic hydrolysis of (XXII) led to amino acid (XXIII), which was converted to the dimethylamino analogue (XXIV) by reductive alkylation under Eschweiler-Clarke conditions. The desired arylpropionic acid (IX) was obtained from (XXIV) by hydrogenolysis in the presence of Pd/C

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
(XXII)	62696	5-methyl-5-[4-(3-methyl-2-thienyl)phenyl]-2,4-imidazolidinedione	C₁₅H₁₄N₂O₂S	详情	详情
(XXIII)	62697	2-[4-(3-methyl-2-thienyl)phenyl]alanine	C₁₄H₁₅NO₂S	详情	详情
(XXIV)	62698	N,N-dimethyl-2-[4-(3-methyl-2-thienyl)phenyl]alanine	C₁₆H₁₉NO₂S	详情	详情

合成路线5

该中间体在本合成路线中的序号：(XIV)

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6

该中间体在本合成路线中的序号：(XIV)

Glycidonitrile (XXXII) was prepared by condensation of ketone (XIV) with chloroacetonitrile (XXXI) under Darzens conditions. Epoxide ring opening in (XXXII) by HCl in toluene provided the chlorohydrin (XXXIII). Acetylation of (XXXIII), followed by dehydrohalogenation led to the acetoxy acrylonitrile (XXXIV). Hydrolysis and decarbonylation of (XXXIV) provided an alternative access to the arylpropionic acid (IX)

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
(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
(XXXI)	14443	2-chloroacetonitrile; chloroacetonitrile	107-14-2	C₂H₂ClN	详情	详情
(XXXII)	62703	3-methyl-3-[4-(3-methyl-2-thienyl)phenyl]-2-oxiranecarbonitrile		C₁₅H₁₃NOS	详情	详情
(XXXIII)	62704	3-chloro-2-hydroxy-3-[4-(3-methyl-2-thienyl)phenyl]butanenitrile		C₁₅H₁₄ClNOS	详情	详情
(XXXIV)	62705	(Z)-1-cyano-2-[4-(3-methyl-2-thienyl)phenyl]-1-propenyl acetate		C₁₇H₁₅NO₂S	详情	详情

合成路线7

该中间体在本合成路线中的序号：(XIV)

A different strategy was based on the Knoevenagel condensation of ketone (XIV) with methyl cyanoacetate (XXXVIII) to produce the alkylidene cyanoacetate (XXXIX). Double-bond epoxidation by means of H2O2 led to (XL), which was further rearranged to keto amide (XLI). Decarboxylation of (XLI) under Hofmann rearrangement conditions furnished the arylpropionic acid (IX)

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
(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
(XXXVIII)	34458	Cyanoacetic acid methyl ester; methyl 2-cyanoacetate	105-34-0	C₄H₅NO₂	详情	详情
(XXXIX)	62709	methyl (E)-2-cyano-3-[4-(3-methyl-2-thienyl)phenyl]-2-butenoate		C₁₇H₁₅NO₂S	详情	详情
(XL)	62710	methyl 2-(aminocarbonyl)-3-methyl-3-[4-(3-methyl-2-thienyl)phenyl]-2-oxiranecarboxylate		C₁₇H₁₇NO₄S	详情	详情
(XLI)	62711	3-[4-(3-methyl-2-thienyl)phenyl]-2-oxobutanamide		C₁₅H₁₅NO₂S	详情	详情

Extended Information