Cesium carbonate → 2-{4-[4-Pyridin-4-YL-1-(2,2,2-trifluoro-ethyl)-1H-pyrazol-3-YL]-phenoxymethyl}-quinoline

HRID 33830

反応式

HRID 33830 の反応式
[N:1]1[CH:6]=[CH:5][C:4]([C:7]2[CH:11]=[N:10][NH:9][C:8]=2[C:12]2[CH:29]=[CH:28][C:15]([O:16][CH2:17][C:18]3[CH:27]=[CH:26][C:25]4[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=4)[N:19]=3)=[CH:14][CH:13]=2)=[CH:3][CH:2]=1.[F:30][C:31]([F:35])([F:34])[CH2:32]I.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C)C=O.O>[N:1]1[CH:2]=[CH:3][C:4]([C:7]2[C:8]([C:12]3[CH:13]=[CH:14][C:15]([O:16][CH2:17][C:18]4[CH:27]=[CH:26][C:25]5[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=5)[N:19]=4)=[CH:28][CH:29]=3)=[N:9][N:10]([CH2:32][C:31]([F:35])([F:34])[F:30])[CH:11]=2)=[CH:5][CH:6]=1

参加物

6

反応物 3

HCID 10796Cesium carbonateHCID 677091,1,1-Trifluoro-2-iodoethaneHCID 116105532-((4-(4-pyridin-4-yl-1H-pyrazol-3-yl)phenoxy)methyl)quinoline

生成物 1

HCID 116482762-{4-[4-Pyridin-4-YL-1-(2,2,2-trifluoro-ethyl)-1H-pyrazol-3-YL]-phenoxymethyl}-quinoline

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒

反応条件

温度
60 °C

実験手順

To a solution of 2-[4-(4-Pyridin4-yl-2H-pyrazol-3-yl)-phenoxymethyl}-quinoline (26.5 g) in dimethyl formamide (140 mL) was added 1,1,1-Trifluoro-2-iodo-ethane (21 mL, 2.0 eq.) and cesium carbonate (68.3 g, 3 eq.) and the reaction mixture heated at 60° C. for 24 h. The reaction mixture was diluted with water, extracted 3× methylene chloride, dried with magnesium sulfate, filtered and concentrated. Purification via flash chromatography eluting with 5% methanol/70% ethyl acetate/hexanes provided the title compound 20.85 g as an 8:1 regioisomeric mixture. Preparative HPLC eluting with acetonitile/methanol (98:2) on a chiralpak AD column with a flow rate of 430 ml/Min provided the pure title compound as a free base 13.4 g. 1H NMR (400 MHz, CDCl3) δ 8.45 (m, 2 H), 8.16 (d, J=8.3 Hz, 1 H), 8.04 (d, J=8.3 Hz, 1H), 7.96 (s, 1H), 7.79 (d, J=8.3 Hz, 1 H), 7.69 (m, 1 H), 7.64 (d, J=8.3 Hz, 1 H), 7.50 (m, 1H), 7.36 (d, J=8.7 Hz, 2 H), 7.14 (d, J=6.2 Hz, 2H), 6.98 (d, J=9.1 Hz, 2 H), 5.35 (s, 2H), 4.75 (q, J=8.3 Hz, 2 H); MS: (M+H m/z=427.1).MS: (M+H m/z=461.2).

後処理

  1. extractionextracted 3× methylene chloride
  2. dry with materialdried with magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customPurification via flash chromatography
  6. washeluting with 5% methanol/70% ethyl acetate/hexanes

出典と根拠

ORDレコード
ord-e953852e14e249ba8839b8b256e16466
出典データセット
uspto-grants-2008_09
特許番号
US07429665B2

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