Dicyclohexylphosphine → N-(5-(4-acetylpiperazin-1-yl)pyridin-2-yl)-2-(3-methyl-2'-(trifluoromethyl)-2,4'-bipyridin-5-yl)acetamide

HRID 592256

反応式

HRID 592256 の反応式
[C:1]([N:4]1[CH2:9][CH2:8][N:7]([C:10]2[CH:11]=[CH:12][C:13]([NH:16][C:17](=[O:27])[CH2:18][C:19]3[CH:20]=[N:21][C:22](Cl)=[C:23]([CH3:25])[CH:24]=3)=[N:14][CH:15]=2)[CH2:6][CH2:5]1)(=[O:3])[CH3:2].[F:28][C:29]([F:40])([F:39])[C:30]1[CH:35]=[C:34](B(O)O)[CH:33]=[CH:32][N:31]=1.C1(PC2CCCCC2)CCCCC1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>CC([O-])=O.CC([O-])=O.[Pd+2]>[C:1]([N:4]1[CH2:9][CH2:8][N:7]([C:10]2[CH:11]=[CH:12][C:13]([NH:16][C:17](=[O:27])[CH2:18][C:19]3[CH:24]=[C:23]([CH3:25])[C:22]([C:34]4[CH:33]=[CH:32][N:31]=[C:30]([C:29]([F:40])([F:39])[F:28])[CH:35]=4)=[N:21][CH:20]=3)=[N:14][CH:15]=2)[CH2:6][CH2:5]1)(=[O:3])[CH3:2]

参加物

6

反応物 4

HCID 13239DicyclohexylphosphineHCID 62657Potassium Phosphate, TribasicHCID 451588802-(Trifluoromethyl)pyridine-4-boronic acidHCID 58447745N-(5-(4-acetylpiperazin-1-yl)pyridin-2-yl)-2-(6-chloro-5-methylpyridin-3-yl)acetamide

生成物 1

HCID 46927436N-(5-(4-acetylpiperazin-1-yl)pyridin-2-yl)-2-(3-methyl-2'-(trifluoromethyl)-2,4'-bipyridin-5-yl)acetamide

試薬・触媒・溶媒 1

HCID 167845palladium(II) acetate触媒

反応条件

温度
120 °C

実験手順

To a sealed tube were added N-(5-(4-acetylpiperazin-1-yl)pyridin-2-yl)-2-(6-chloro-5-methylpyridin-3-yl)acetamide 148-1 (123 mg, 0.32 mmol), 2-(trifluoromethyl)pyridin-4-ylboronic acid (61 mg, 0.32 mmol), Pd(OAc)2 (3.6 mg, 0.016 mmol), 2,6-Dimethoxy-1,1′-biphenyl-2-yl)dicyclohexylphosphine (13.0 mg, 0.032 mmol) and K3PO4 (202 mg, 0.95 mmol). The tube and its contents were then purged with nitrogen. After degassed toluene (1.0 mL) was added, the mixture was stirred at 120° C. overnight. After cooling to room temperature, the mixture was poured into water and extracted with ethyl acetate (8 mL×3). The combined organic phases were dried over Na2SO4, and concentrated. The residue was purified by reverse phase HPLC to give to give N-(5-(4-acetylpiperazin-1-yl)pyridin-2-yl)-2-(3-methyl-2′-(trifluoromethyl)-2,4′-bipyridin-5-yl)acetamide 222. MS m/z 498.8 (M+1); 1H NMR 400 MHz (CDCl3) δ 8.81 (d, 1H), 8.51 (d, 1H), 8.35 (s, 1H), 8.11 (d, 1H), 7.91 (s, 1H), 7.89 (s, 1H), 7.68-7.64 (m, 2H), 7.30 (dd, 1H), 3.80-3.75 (m, 4H), 3.63 (t, 2H), 3.14 (t, 2H), 3.11 (t, 2H), 2.39 (s, 3H), 2.14 (s, 3H).

後処理

  1. customThe tube and its contents were then purged with nitrogen
  2. customAfter degassed toluene (1.0 mL)
  3. additionwas added
  4. temperatureAfter cooling to room temperature
  5. additionthe mixture was poured into water
  6. extractionextracted with ethyl acetate (8 mL×3)
  7. dry with materialThe combined organic phases were dried over Na2SO4
  8. concentrationconcentrated
  9. customThe residue was purified by reverse phase HPLC
  10. customto give

出典と根拠

ORDレコード
ord-2adfe1667539432b96d0272186bd9df8
出典データセット
uspto-grants-2016_01
特許番号
US09238646B2

関連ノート

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