1,2-Dichloroethane → 1-(5-Fluoropyridin-2-yl)-N-{(1R)-1-[1-oxido-6-(trifluoromethyl)pyridin-3-yl]ethyl}-3-phenyl-1H-pyrazole-4-carboxamide

HRID 1842566노트

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HRID 1842566 반응식
[F:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[CH:12]=[C:11]([C:13]([OH:15])=O)[C:10]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)=[N:9]2)=[N:6][CH:7]=1.[O-:22][N+:23]1[C:28]([C:29]([F:32])([F:31])[F:30])=[CH:27][CH:26]=[C:25]([C@H:33]([NH2:35])[CH3:34])[CH:24]=1.C(Cl)CCl.C1C=NC2N(O)N=NC=2C=1.C(N(CC)CC)C>CN(C=O)C>[F:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[CH:12]=[C:11]([C:13]([NH:35][C@@H:33]([C:25]3[CH:24]=[N+:23]([O-:22])[C:28]([C:29]([F:30])([F:31])[F:32])=[CH:27][CH:26]=3)[CH3:34])=[O:15])[C:10]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)=[N:9]2)=[N:6][CH:7]=1

참가 물질

7

반응물 5

HCID 111,2-DichloroethaneHCID 8471TriethylamineHCID 181649HOAtHCID 59539683(1R)-1-[1-oxido-6-(trifluoromethyl)pyridin-3-yl]ethanamineHCID 666794871-(5-Fluoropyridin-2-yl)-3-phenyl-1H-pyrazole-4-carboxylic acid

생성물 1

HCID 469180871-(5-Fluoropyridin-2-yl)-N-{(1R)-1-[1-oxido-6-(trifluoromethyl)pyridin-3-yl]ethyl}-3-phenyl-1H-pyrazole-4-carboxamide수율 88.7%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

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온도
50 °C

실험 절차

To a solution of 1-(5-fluoropyridin-2-yl)-3-phenyl-1H-pyrazole-4-carboxylic acid (0.10 g, 0.22 mmol) in DMF (1 mL) were added (1R)-1-[1-oxido-6-(trifluoromethyl)pyridin-3-yl]ethanamine (63.5 mg, 0.26 mmol), EDC (73.2 mg, 0.38 mmol), HOAT (14.8 mg, 0.11 mmol) and triethylamine (0.12 mL, 0.87 mmol). The mixture was stirred at 50° C. After 3 h, the mixture was filtered. The filtrate was purified by reverse phase chromatography (C-18, 95% water/acetonitrile→5% water/acetonitrile with 0.1% ammonium hydroxide) and gave the title compound (92 mg). The mixture was converted to hydrochloride salt using HCl (4.0 M in dioxane). HRMS 472.1410 (M+1). 1H NMR (500 MHz, DMSO): 9.25 (s, 1H); 8.89 (d, J=7.2 Hz, 1H); 8.60 (d, J=2.8 Hz, 1H); 8.54 (s, 1H); 8.09 (dd, J=9.0, 3.9 Hz, 1H); 8.02 (td, J=8.5, 2.9 Hz, 1H); 7.94 (d, J=8.4 Hz, 1H); 7.79-7.76 (m, 2H); 7.54 (d, J=8.4 Hz, 1H); 7.40 (t, J=3.1 Hz, 3H); 5.13-5.06 (m, 1H); 1.48 (d, J=7.1 Hz, 3H).

후처리

  1. filtrationthe mixture was filtered
  2. customThe filtrate was purified by reverse phase chromatography (C-18, 95% water/acetonitrile→5% water/acetonitrile with 0.1% ammonium hydroxide)

출처 및 근거

ORD 기록
ord-0b4d17e6a40244c096616b7554928836
출처 데이터셋
uspto-grants-2015_02
특허 번호
US08946231B2

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