HCID 71014126、化合物 → HCID 71014159、化合物

HRID 1430081ノート

反応式

HRID 1430081 の反応式
Cl[C:2]1[CH:7]=[CH:6][N:5]=[C:4]([C:8]2([F:36])[CH2:13][CH2:12][N:11]([CH2:14][C:15]3[C:24]4[C:19](=[C:20]([F:25])[CH:21]=[CH:22][CH:23]=4)[N:18]=[C:17]([C:26]([NH:28][C@H:29]4[CH2:34][CH2:33][CH2:32][CH2:31][C@@H:30]4[OH:35])=[O:27])[CH:16]=3)[CH2:10][CH2:9]2)[CH:3]=1.[CH3:37][Zn]C>C1COCC1.C(OCC)(=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:25][C:20]1[CH:21]=[CH:22][CH:23]=[C:24]2[C:19]=1[N:18]=[C:17]([C:26]([NH:28][C@H:29]1[CH2:34][CH2:33][CH2:32][CH2:31][C@@H:30]1[OH:35])=[O:27])[CH:16]=[C:15]2[CH2:14][N:11]1[CH2:12][CH2:13][C:8]([F:36])([C:4]2[CH:3]=[C:2]([CH3:37])[CH:7]=[CH:6][N:5]=2)[CH2:9][CH2:10]1

参加物

6

反応物 2

HCID 71014126HCID 71014126、化合物HCID 178477796HCID 178477796、化合物2 回

生成物 1

HCID 71014159HCID 71014159、化合物

試薬・触媒・溶媒 3

HCID 178418397HCID 178418397、化合物触媒2 回HCID 8028Tetrahydrofuran溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
90 °C

実験手順

To a solution of 4-{[4-(4-chloropyridin-2-yl)-4-fluoropiperidin-1-yl]methyl}-8-fluoro-N-[(1S,2S)-2-hydroxycyclohexyl]quinoline-2-carboxamide (Example C) (0.022 g, 0.043 mmol) in THF (3 mL) under an atmosphere of nitrogen was added dimethyl zinc (2.0 M in THF, 0.043 mL, 0.085 mmol) and tetrakis(triphenylphosphine)palladium(0) (0.0011 mg, 0.00090 mmol). The reaction was heated to 90° C., cooled to RT, and retreated with additional dimethyl zinc (2.0 M in THF, 0.043 mL, 0.085 mmol) and tetrakis(triphenylphosphine)palladium(0) (0.0011 mg, 0.00090 mmol). The reaction was heated to 100° C. for 5 h, then at 50° C. for an additional 16 h. The mixture was cooled to RT, diluted with ethyl acetate, and washed with saturated aqueous sodium bicarbonate and brine. The organic solution was dried over sodium sulfate, filtered, and concentrated in vacuo. The resultant residue was purified via silica gel chromatography eluting with 0-5% MeOH in dichloromethane to provide the title compound (Example D) as a white solid that gave a proton NMR spectra consistent with theory and a mass ion (ES+) of 495.1 for M+H+. 1H NMR (400 MHz, CDCl3) δ 8.39-8.36 (m, 2H), 8.30-8.20 (m, 2H), 7.69-7.38 (m, 3H), 7.00 (br s, 1H), 4.03 (s, 2H), 3.89 (br s, 1H), 3.59-3.49 (m, 1H), 3.48-3.14 (m, 1H), 2.85-2.81 (m, 2H), 2.61-2.57 (m, 2H), 2.44-2.37 (m, 2H), 2.37 (s, 3H), 2.18-2.13 (m, 2H), 1.87-1.79 (m, 4H), 1.50-1.14 (m, 4H).

後処理

  1. temperaturecooled to RT
  2. temperatureThe reaction was heated to 100° C. for 5 h
  3. temperatureThe mixture was cooled to RT
  4. washwashed with saturated aqueous sodium bicarbonate and brine
  5. dry with materialThe organic solution was dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe resultant residue was purified via silica gel chromatography
  9. washeluting with 0-5% MeOH in dichloromethane

出典と根拠

ORDレコード
ord-69a2dc7f56ff48b7a543de2ed4568672
出典データセット
uspto-grants-2015_01
特許番号
US08940765B2

反応ノート

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