Prinomide triethanolamine, CGS-10787B, -Drug Synthesis Database

【结构式】

【药物名称】Prinomide triethanolamine, CGS-10787B

【化学名称】2-(2-Cyano-2-phenylaminocarbonyl)acetyl-1-methylpyrrol triethanolamine salt

【CA登记号】77639-66-8 (free base)

【分子式】C₂₁H₂₈N₄O₅

【分子量】416.48111

【开发单位】Novartis (Originator)

【药理作用】ANALGESIC AND ANESTHETIC DRUGS, Analgesic Drugs, Non-Opioid Analgesics, Non-Steroidal Antiinflammatory Drugs

合成路线1 合成路线2 合成路线3

合成路线1

The synthesis of [14C]-labeled prinomide has been described: The carboxylation of 1-methylpyrrole (I) with 14CO2 and butyllithium in THF gives labeled 1-methylpyrrole-2-carboxylic acid (II), which is esterified with diazomethane to the methyl ester (III). The reaction of (III) with acetonitrile by means of NaH in DMF affords 3-(1-methylpyrrol-2-yl)-3-oxopropanenitrile (IV) labeled in the carbonyl group. Finally, this compound is condensed with phenylisocyanate (V) by means of triethylamine in toluene, affording the prinomide labeled in the carbonyl group. The condensation of unlabeled (IV) with (V) labeled in the phenyl ring yields the corresponding prinomide labeled in the aromatic ring.

参考文献中间体

【1】 Chaudhuri, N.K.; Markus, B.; Synthesis of two 14C-labeled forms of prinomide, a potential anti-inflammatory compound and its hydroxy metabolite, labeled with 14C. J Label Compd Radiopharm 1990, 28, 3, 321.

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)	11285	1-Methyl-1H-pyrrole; Methylpyrrole	96-54-8	C₅H₇N	详情	详情
(II)	11286	1-Methyl-1H-pyrrole-2-carboxylic acid; 1-Methyl-2-pyrrolecarboxylic acid	6973-60-0	C₆H₇NO₂	详情	详情
(II)	45058	1-methyl-1H-pyrrole-2-carboxylic acid		C₆H₇NO₂	详情	详情
(III)	11287	methyl 1-methyl-1H-pyrrole-2-carboxylate	37619-24-2	C₇H₉NO₂	详情	详情
(III)	45059	methyl 1-methyl-1H-pyrrole-2-carboxylate		C₇H₉NO₂	详情	详情
(IV)	11288	3-(1-Methyl-1H-pyrrol-2-yl)-3-oxopropanenitrile		C₈H₈N₂O	详情	详情
(IV)	45060	3-(1-methyl-1H-pyrrol-2-yl)-3-oxopropanenitrile		C₈H₈N₂O	详情	详情
(V)	11289	1-Isocyanatobenzene; phenyl isocyanate; Phenylisocyanate	103-71-9	C₇H₅NO	详情	详情

合成路线2

The esterification of N-methylpyrrol-2-carboxylic acid (I) with NaH and methyl iodide in DMF gives methyl N methylpyrrol 2 carboxylate (II), which is condensed with acetonitrile by means of NaH in DMF yielding 3-(1-methyl-2-pyrrolyl)-3-oxopropionitrile (III). The reaction of (III) with phenylisocyanate (IV) by means of triethylamine in toluene affords 2-cyano-3-(1-methyl-2-pyrrolyl)-3-oxo-N-phenylpropionamide (V), which is finally treated with triethanolamine (VI) in hot ethanol.

参考文献中间体

【1】 Walker, G.N. (Novartis AG); alpha-Carbamoyl-pyrrolpropionitriles, process fortheir preparation and pharmaceutical preparations containing them. EP 0143142 .
【2】 Serradell, M.N.; Castaner, J.; Castaner, R.M.; Prinomide Triethanolamine. Drugs Fut 1987, 12, 8, 773.

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)	11286	1-Methyl-1H-pyrrole-2-carboxylic acid; 1-Methyl-2-pyrrolecarboxylic acid	6973-60-0	C₆H₇NO₂	详情	详情
(II)	11287	methyl 1-methyl-1H-pyrrole-2-carboxylate	37619-24-2	C₇H₉NO₂	详情	详情
(III)	11288	3-(1-Methyl-1H-pyrrol-2-yl)-3-oxopropanenitrile		C₈H₈N₂O	详情	详情
(IV)	11289	1-Isocyanatobenzene; phenyl isocyanate; Phenylisocyanate	103-71-9	C₇H₅NO	详情	详情
(V)	28167	2-cyano-3-(1-methyl-1H-pyrrol-2-yl)-3-oxo-N-phenylpropanamide		C₁₅H₁₃N₃O₂	详情	详情
(VI)	28168	2-[bis(2-hydroxyethyl)amino]-1-ethanol	102-71-6	C₆H₁₅NO₃	详情	详情

合成路线3

The reaction of acid (I) with SOCl2 in ethyl ether containing triethylamine gives the corresponding acyl chloride (VII), which is condensed with ethyl cyanacetate (VIII) by means of NaH in glyme yielding ethyl 2-cyano-3-(1-methyl-2-pyrrolyl)-3-oxopropanoate (IX). The reaction of (IX) with aniline (X) in refluxing xylene affords the corresponding anilide (V) already obtained.

参考文献中间体

【1】 Walker, G.N. (Novartis AG); alpha-Carbamoyl-pyrrolpropionitriles, process fortheir preparation and pharmaceutical preparations containing them. EP 0143142 .
【2】 Serradell, M.N.; Castaner, J.; Castaner, R.M.; Prinomide Triethanolamine. Drugs Fut 1987, 12, 8, 773.

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)	11286	1-Methyl-1H-pyrrole-2-carboxylic acid; 1-Methyl-2-pyrrolecarboxylic acid	6973-60-0	C₆H₇NO₂	详情	详情
(V)	28167	2-cyano-3-(1-methyl-1H-pyrrol-2-yl)-3-oxo-N-phenylpropanamide		C₁₅H₁₃N₃O₂	详情	详情
(VI)	28168	2-[bis(2-hydroxyethyl)amino]-1-ethanol	102-71-6	C₆H₁₅NO₃	详情	详情
(VII)	28169	1-methyl-1H-pyrrole-2-carbonyl chloride		C₆H₆ClNO	详情	详情
(VIII)	11877	Cyanoacetic acid ethyl ester; Ethyl 2-cyanoacetate; Ethyl cyanoacetate; Ethyl isocyanacetate	105-56-6	C₅H₇NO₂	详情	详情
(IX)	28170	ethyl 2-cyano-3-(1-methyl-1H-pyrrol-2-yl)-3-oxopropanoate		C₁₁H₁₂N₂O₃	详情	详情
(X)	12294	Aniline; Phenylamine	62-53-3	C₆H₇N	详情	详情

Extended Information