Alminoprofen, EB-382, Minalfene, -Drug Synthesis Database

【结构式】

【药物名称】Alminoprofen, EB-382, Minalfene

【化学名称】p-[(2-Methylallyl)amino]hydratropic acid
　　　　　　2-[4-(2-Methylallylamino)phenyl]propionic acid
　　　　　　alpha-Methyl-4-[(2-methyl-2-propenyl)amino]benzeneacetic acid

【CA登记号】39718-89-3

【分子式】C₁₃H₁₇NO₂

【分子量】219.28594

【开发单位】Bouchara (Not Determined), Morishita (Not Determined), UCB Japan (Not Determined)

【药理作用】Non-Steroidal Antiinflammatory Drugs

合成路线1 合成路线2

合成路线1

The malonic synthesis of 4-nitrochlorobenzene (VIII) with sodium diethyl methylmalonate (IX) (prepared with the corresponding malonic ester and NaH) in hot DMF gives diethyl (4-nitrophenyl)methylmalonate (X), which is reduced with H2 over Pd/C as before yielding diethyl (4-aminophenyl)methylmalonate (XI). The alkylation of (XI) with (VI) by means of NaHCO3 in refluxing ethanol affords diethyl [4-(2-methylallyl)aminophenyl]methylmalonate (XII), which is treated with sodium ethoxide in refluxing ethanol to yield ethyl 2-(4-[2-methylallylamino)phenyl]propionate (XIV). Finally, this compound is hydrolyzed with NaOH in refluxing ethanol. Partial hydrolysis of (XII) with NaOH in refluxing ethanol gives 2-[4-(2-methylallylamino)phenyl]methylmalonic acid (XIII), which is finally decarboxylated by treatment with refluxing aqueous HCl. The simultaneous hydrolysis and decarboxylation of (XII) with NaOH in refluxing ethanol also gives the title product.

参考文献中间体

【1】 Dumaitre, B.; et al.; Synthesis of some analgesic and antiinflammatory 4-aminophenylacetic and 4-aminophenylacetic and 2-(4-aminophenyl)propionic acid derivatives. Eur J Med Chem - Chim Ther 1979, 14, 3, 207-214.
【2】 Serradell, M.N.; Castaner, J.; Alminoprofen. Drugs Fut 1984, 9, 3, 165.

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)	12127	3-Chloro-2-methyl-1-propene; Isobutenyl chloride	563-47-3	C₄H₇Cl	详情	详情
(VIII)	13909	1-Chloro-4-nitrobenzene; p-Nitrochlorobenzene	100-00-5	C₆H₄ClNO₂	详情	详情
(IX)	30310	diethyl 2-methylmalonate	609-08-5	C₈H₁₄O₄	详情	详情
(X)	13910	diethyl 2-methyl-2-(4-nitrophenyl)malonate		C₁₄H₁₇NO₆	详情	详情
(XI)	30311	diethyl 2-(4-aminophenyl)-2-methylmalonate		C₁₄H₁₉NO₄	详情	详情
(XII)	30312	diethyl 2-methyl-2-[4-[(2-methyl-2-propenyl)amino]phenyl]malonate		C₁₈H₂₅NO₄	详情	详情
(XIII)	30313	2-methyl-2-[4-[(2-methyl-2-propenyl)amino]phenyl]malonic acid		C₁₄H₁₇NO₄	详情	详情
(XIV)	30314	ethyl 2-[4-[(2-methyl-2-propenyl)amino]phenyl]propanoate		C₁₅H₂₁NO₂	详情	详情

合成路线2

The reaction of 4-nitrophenylacetic acid (I) with formaldehyde and dimethylamine in water gives 2-(4-nitrophenyl)-3-(dimethylamino)propionic acid (II), which by treatment with refluxing concentrated HCl is converted into 2-(4-nitrophenyl)acrylic acid (III). The esterification of (III) with methanol and p-toluenesulfonic acid yields the corresponding methyl ester (IV), which is reduced with H2 over Pd/C in ethanol to afford methyl 2-(4-aminophenyl)propionate (V). The alkylation of (V) with 2-methylallyl chloride (VI) by means of pyridine in refluxing ethanol gives methyl 2-[4-(2-methylallylamino)phenyl]propionate (VII), which is finally hydrolyzed with NaOH in refluxing methanol.

参考文献中间体

【1】 Dumaitre, B.; et al.; Synthesis of some analgesic and antiinflammatory 4-aminophenylacetic and 4-aminophenylacetic and 2-(4-aminophenyl)propionic acid derivatives. Eur J Med Chem - Chim Ther 1979, 14, 3, 207-214.
【2】 Bouchara, E. (Laboratoires du Dr. E. Bouchara); Nouveau procede de preparation de derives de l'acide phenylacetique. FR 2289180 .
【3】 Serradell, M.N.; Castaner, J.; Alminoprofen. Drugs Fut 1984, 9, 3, 165.

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)	30305	2-(4-nitrophenyl)acetic acid	104-03-0	C₈H₇NO₄	详情	详情
(II)	30306	N,N-dimethyl-2-(4-nitrophenyl)-beta-alanine		C₁₁H₁₄N₂O₄	详情	详情
(III)	30307	2-(4-nitrophenyl)acrylic acid		C₉H₇NO₄	详情	详情
(IV)	30308	methyl 2-(4-nitrophenyl)acrylate		C₁₀H₉NO₄	详情	详情
(V)	13912	methyl 2-(4-aminophenyl)propanoate	39718-97-3	C₁₀H₁₃NO₂	详情	详情
(VI)	12127	3-Chloro-2-methyl-1-propene; Isobutenyl chloride	563-47-3	C₄H₇Cl	详情	详情
(VII)	30309	methyl 2-[4-[(2-methyl-2-propenyl)amino]phenyl]propanoate		C₁₄H₁₉NO₂	详情	详情

Extended Information