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

HRID 81024

반응식

HRID 81024 반응식
[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]

참가 물질

7

반응물 3

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

생성물 1

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

시약·촉매·용매 3

HCID 11979704Tetrakis(triphenylphosphine)palladium촉매HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

반응 조건

온도
90 °C

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-a6e7388cbfb74c399b7990b730d021b8
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08846673B2

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