2-(trifluoromethyl)benzaldehyde -Drug Synthesis Database

【结构式】

【分子编号】30332

【品名】2-(trifluoromethyl)benzaldehyde

【CA登记号】447-61-0

【分子式】C₈H₅F₃O

【分子量】174.1223096

【元素组成】C 55.18% H 2.89% F 32.73% O 9.19%

与该中间体有关的原料药合成路线共 3 条

合成路线1 合成路线2 合成路线3

合成路线1

该中间体在本合成路线中的序号：(I)

This compound can be obtained by two different ways: 1) By cyclization of 2-trifluoromethylbenzaldehyde (I) with methyl 3-amino crotonate (II) and nitropropanone (III) in refluxing ethanol. 2) By cyclization of methyl 2-(2-trifluoromethylbenzylidene)acetoacetate (IV) with 2-amino-1-nitropropene (V) in refluxing ethanol.

参考文献中间体

合成目标

【1】 Bossert, F.; Franckowiak, G.; Heise, A.; Kazda, S.; Meyer, H.; Stoepel, K.; Towart, R.; Wehinger, E. (Bayer AG); Nitro-substituted 1,4-dihydropyridines, processes for their production and their medicinal use. DE 2752820; EP 0002208; ES 475379; ES 480350; ES 480351; JP 54081279 .
【2】 Bossert, F.; Franckowiak, G.; Boeshagen, H.; Goldmann, S.; Schramm, M.; Thomas, G.; Meyer, H.; Towart, R.; Wehinger, E. (Bayer AG); Dihydropyridines having a positive inotropic effect, novel compounds, their use in medicaments, and processes for their preparation. BE 0893984; DE 3130041; ZA 8205456 .
【3】 Castaner, J.; Serradell, M.N.; BAY-K-8644. Drugs Fut 1984, 9, 3, 168.

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)	30332	2-(trifluoromethyl)benzaldehyde	447-61-0	C₈H₅F₃O	详情	详情
(II)	11372	Methyl (E)-3-amino-2-butenoate; Methyl 3-aminocrotonate		C₅H₉NO₂	详情	详情
(III)	30333	1-nitroacetone		C₃H₅NO₃	详情	详情
(IV)	30334	methyl (Z)-2-acetyl-3-[2-(trifluoromethyl)phenyl]-2-propenoate		C₁₃H₁₁F₃O₃	详情	详情
(V)	30335	(E)-1-methyl-2-nitroethenylamine; (E)-1-nitro-1-propen-2-amine		C₃H₆N₂O₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VIIII)

D-Threonine (I) was esterified by means of thionyl chloride in methanol, and the resultant amino ester (II) was subsequently acylated with 3,5-dinitrobenzoyl chloride (III) to afford amide (IV). Conversion of (IV) to the acetoacetate ester (VI) was effected by reaction with the diketene precursor 2,2,6-trimethyl-4H-1,3-dioxin-4-one (V) in boiling xylene. Treatment of keto ester (V) with ammonia in the presence of p-toluenesulfonic acid produced the aminocrotonate ester (VI). Dihydropyridine (IXa-b) was then obtained as a diastereomeric mixture by a modified Hantzsh condensation between enamine (VI), 2-trifluoromethylbenzaldehyde (VII) and nitroacetone. After chromatographic separation of the isomers, the chiral auxiliary group was removed by methanolysis in the presence of DBU. The desired (+)-(S)-dihydropyridinecarboxylic acid (X) was finally converted to the nitrooxyethyl ester by reaction with 2-bromoethyl nitrate (XI).

参考文献中间体

合成目标

【1】 Shan, R.; Knaus, E.E.; Howlett, S.E.; Syntheses, calcium channel agonist-antagonist modulation activities, nitric oxide release, and voltage-clamp studies of 2-nitrooxyethyl 1,4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluoromethylphenyl)pyridine-5-carboxylate enantiomers. J Med Chem 2002, 45, 4, 955.
【2】 Knaus, E.E.; Shan, R.; The design of (-)-(S)-nitrooxyethyl 1,4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluoromethylphenyl)pyridine-5-carboxylate: A cardioselective positive inotropic derivative of Bay K 8644. Bioorg Med Chem Lett 1999, 9, 17, 2613.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(VIIII)	30332	2-(trifluoromethyl)benzaldehyde	447-61-0	C₈H₅F₃O	详情	详情
(IXa)	59607	(1S,2R)-2-[(3,5-dinitrobenzoyl)amino]-3-methoxy-1-methyl-3-oxopropyl (4S)-2,6-dimethyl-5-nitro-4-[2-(trifluoromethyl)phenyl]-1,4-dihydro-3-pyridinecarboxylate		C₂₇H₂₄F₃N₅O₁₁	详情	详情
(IXb)	59608	(1S,2R)-2-[(3,5-dinitrobenzoyl)amino]-3-methoxy-1-methyl-3-oxopropyl (4R)-2,6-dimethyl-5-nitro-4-[2-(trifluoromethyl)phenyl]-1,4-dihydro-3-pyridinecarboxylate		C₂₇H₂₄F₃N₅O₁₁	详情	详情
(I)	28908	L-Threonine; (2R,3S)-2-amino-3-hydroxybutyric acid	632-20-2	C₄H₉NO₃	详情	详情
(II)	42026	methyl (2S,3R)-2-amino-3-hydroxybutanoate		C₅H₁₁NO₃	详情	详情
(III)	12053	3,5-Dinitrobenzoyl chloride	99-33-2	C₇H₃ClN₂O₅	详情	详情
(IV)	59604	methyl (2R,3S)-2-[(3,5-dinitrobenzoyl)amino]-3-hydroxybutanoate		C₁₂H₁₃N₃O₈	详情	详情
(V)	13327	2,2,6-Trimethyl-4H-1,3-dioxin-4-one；2,2,6-trimethyl-1,3-dioxin-4-one；2,2,6-trimethyl-m-Dioxin-4-one;3-(1-hydroxy-1-methylethoxy)-d-lactone Crotonicacid	5394-63-8	C₇H₁₀O₃	详情	详情
(VI)	59605	methyl (2R,3S)-3-(acetoacetyloxy)-2-[(3,5-dinitrobenzoyl)amino]butanoate		C₁₆H₁₇N₃O₁₀	详情	详情
(VII)	59606	(1S,2R)-2-[(3,5-dinitrobenzoyl)amino]-3-methoxy-1-methyl-3-oxopropyl (E)-3-amino-2-butenoate		C₁₆H₁₈N₄O₉	详情	详情
(X)	59609	(4S)-2,6-dimethyl-5-nitro-4-[2-(trifluoromethyl)phenyl]-1,4-dihydro-3-pyridinecarboxylic acid		C₁₅H₁₃F₃N₂O₄	详情	详情
(XI)	59610	1-bromo-2-(nitrooxy)ethane		C₂H₄BrNO₃	详情	详情

合成路线3

该中间体在本合成路线中的序号：(II)

By cyclization of ethyl acetoacetate (I) with 2-trifluoromethylbenzaldehyde (II) and N-(2-aminoethyl)morpholine (III) in refluxing ethanol

参考文献中间体

合成目标

【1】 Blancafort, P.; Serradell, M.N.; Castaner, J.; Thorpe, P.J.; Flordipine. Drugs Fut 1983, 8, 9, 770.
【2】 Loev, B.; Shroff, J.R. (USV Pharmaceutical Corp.); BE 888327; DE 3109794; FR 2480284; GB 2073739; JP 81158762; US 4258042 .

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)	11819	ethyl acetoacetate; ethyl 3-oxobutanoate；Acetoacetic ester;Ethyl beta-ketobutyrate;ethyl 3-oxobutyrate	141-97-9	C₆H₁₀O₃	详情	详情
(II)	30332	2-(trifluoromethyl)benzaldehyde	447-61-0	C₈H₅F₃O	详情	详情
(III)	12880	4-(2-Aminoethyl)morpholine; 2-(4-Morpholinyl)ethylamine; 2-(4-Morpholinyl)-1-ethanamine; N-(2-Aminoethyl)morpholine; N-Morpholine ethanamide	2038-03-1	C₆H₁₄N₂O	详情	详情

Extended Information