methyl 2-(4-aminophenyl)propanoate -Drug Synthesis Database

【结构式】

【分子编号】13912

【品名】methyl 2-(4-aminophenyl)propanoate

【CA登记号】39718-97-3

【分子式】C₁₀H₁₃NO₂

【分子量】179.21876

【元素组成】C 67.02% H 7.31% N 7.82% O 17.85%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(V)

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

合成目标

【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

合成路线2

该中间体在本合成路线中的序号：(IV)

Camprofen has been synthesized previously by Picciola as a chemical intermediate in the preparation of an indazolylpropionic acid, but was apparently not itself evaluated for antiinflammatory activity during that study. The synthetic approach (scheme 16191901a), begins with 1-chloro-4-nitrobenzene (I), which is readily available commercially. Treatment of (I) with the carbanion derived from diethyl methylmalonate (using sodium hydride as base, in N,N-dimethylformamide) provides the intermediate diethyl ester (II), which is saponified in situ and then acidified to the acid (IIIa). Crude (IIIa) is then esterified to the methyl ester (IIIb), purified by column chromatography, the sequence being analogous to that of Hino et al. The nitrophenyl ester (IIIb) is dissolved in 95% ethanol and hydrogenated in the presence of palladium catalyst to provide the 4-aminophenyl compound (IV). Finally, an Ullmann-Jourdan condensation of (IV) with 2-chlorobenzoic acid in the presence of anhydrous potassium carbonate, activated copper powder and N,N-methylformamide provides camprofen. This synthetic scheme uses cheap and readily available reagents and provides racemic camprofen in an overall yield of 52% based on 1-chloro-4-nitrobenzene (I).

参考文献中间体

合成目标

【1】 Appleton, R.A.; Brown, K.; Conformational requirements at the prostaglandin cyclooxygenase receptor site: A template for designing non-steroidal anti-inflammatory drugs. Prostaglandins 1979, 18, 29.
【2】 Hino, K.; Nakamura, H.; Nagai, Y.; Uno, H.; Nishimura, H.; Non-steroidal anti-inflammatory agents. 2.[(heteroarylamino)phenyl]alkanoic acids. J Med Chem 1983, 26, 222.
【3】 Taraporewala, I.B.; Kauffman, J.M.; Synthesis and structure activity relationships of anti-inflammatory 9,10-dihydro-9-oxo-2-acridine-alkanoic acids and 4-(2-carboxyphenyl)aminobenzenealkanoic acids. J Pharm Sci 1990, 79, 2, 173.
【4】 Kauffman, J.M.; Taraporewala, I.B.; Synthesis of the p-nitrophenyl ester of acridine-2-acetic acid. J Heterocycl Chem 1982, 19, 1557.
【5】 Picciola, G.; Heterocyclic compounds containing 4-aminophenyl-alkanoic acid residues with potential antiinflammatory activity. III. Derivatives of 3-hydroxyindazole. Boll Chim Farm 1981, 120, 8, 458.
【6】 Taraporewala, I.B.; Kauffman, J.M.; CAMPROFEN. Drugs Fut 1990, 15, 6, 563.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	10203	o-Chlorobenzoic acid; 2-Chlorobenzoic acid	118-91-2	C₇H₅ClO₂	详情	详情
	33989			C₈H₁₃NaO₄	详情	详情
(III-b)	13911	methyl 2-(4-nitrophenyl)propanoate		C₁₀H₁₁NO₄	详情	详情
(III-a)	52520	2-(4-nitrophenyl)propanoic acid		C₉H₉NO₄	详情	详情
(I)	13909	1-Chloro-4-nitrobenzene; p-Nitrochlorobenzene	100-00-5	C₆H₄ClNO₂	详情	详情
(II)	13910	diethyl 2-methyl-2-(4-nitrophenyl)malonate		C₁₄H₁₇NO₆	详情	详情
(IV)	13912	methyl 2-(4-aminophenyl)propanoate	39718-97-3	C₁₀H₁₃NO₂	详情	详情

Extended Information