(3-Acetamidophenyl)boronic acid → N-(3-(6-chloro-5-cyano-4-(4-phenoxyphenyl)pyridin-2-yl)phenyl)acetamide

HRID 81024

反応式

HRID 81024 の反応式
[Cl:1][C:2]1[N:9]=[C:8](Cl)[CH:7]=[C:6]([C:11]2[CH:16]=[CH:15][C:14]([O:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)=[CH:13][CH:12]=2)[C:3]=1[C:4]#[N:5].[C:24]([NH:27][C:28]1[CH:29]=[C:30](B(O)O)[CH:31]=[CH:32][CH:33]=1)(=[O:26])[CH3:25].O.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>CN(C)C=O.C(OCC)(=O)C.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Pd]>[Cl:1][C:2]1[N:9]=[C:8]([C:32]2[CH:33]=[C:28]([NH:27][C:24](=[O:26])[CH3:25])[CH:29]=[CH:30][CH:31]=2)[CH:7]=[C:6]([C:11]2[CH:12]=[CH:13][C:14]([O:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)=[CH:15][CH:16]=2)[C:3]=1[C:4]#[N:5]

参加物

7

反応物 3

HCID 157274(3-Acetamidophenyl)boronic acidHCID 22031701Potassium phosphate, tribasic, monohydrateHCID 866656822,6-Dichloro-4-(4-phenoxyphenyl)nicotinonitrile

生成物 1

HCID 86665685N-(3-(6-chloro-5-cyano-4-(4-phenoxyphenyl)pyridin-2-yl)phenyl)acetamide収率 42.7%

試薬・触媒・溶媒 3

HCID 11979704Tetrakis(triphenylphosphine)palladium触媒HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
90 °C

実験手順

A mixture of 2,6-dichloro-4-(4-phenoxyphenyl)nicotinonitrile (51 mg, 0.149 mmol, from Step 2 of Example 8), 3-acetamidophenylboronic acid (29.4 mg, 0.164 mmol), palladium tetrakis(triphenylphosphine) (15.12 mg, 0.015 mmol) and potassium phosphate tribasic monohydrate (0.299 mL, 0.598 mmol) in N,N-dimethylformamide (1.5 mL) was heated to 90° C. under nitrogen for 2 h. After cooling to room temperature, the mixture was diluted with ethyl acetate (80 mL), washed with water (10 mL), brine (10 mL), dried (MgSO4) and concentrated. Silica gel chromatography, eluting with 5-40% ethyl acetate in hexanes, gave N-(3-(6-chloro-5-cyano-4-(4-phenoxyphenyl)pyridin-2-yl)phenyl)acetamide as white solid (28 mg, 42% yield). 1H NMR (400 MHz, CDCl3) δ ppm 8.26 (1H, s), 7.79-7.89 (1H, m), 7.77 (1H, s), 7.67-7.73 (1H, m), 7.58-7.66 (2H, m), 7.50-7.57 (1H, m), 7.37-7.47 (3H, m), 7.17-7.24 (1H, m), 7.05-7.16 (4H, m), 2.22 (3H, s); MS (ES+) m/z: 440 (M±H); LC retention time: 4.165 min (analytical HPLC Method A).

後処理

  1. temperatureAfter cooling to room temperature
  2. washwashed with water (10 mL), brine (10 mL)
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated
  5. washSilica gel chromatography, eluting with 5-40% ethyl acetate in hexanes

出典と根拠

ORDレコード
ord-a6e7388cbfb74c399b7990b730d021b8
出典データセット
uspto-grants-2014_09
特許番号
US08846673B2

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