Potassium Phosphate, Tribasic → 1-(4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenyl)-4-(4-(trifluoromethoxy)-phenyl)pyridin-2(1H)-one

HRID 1044409

反応式

HRID 1044409 の反応式
Cl[C:2]1[CH:7]=[CH:6][N:5]([C:8]2[CH:13]=[CH:12][C:11]([O:14][CH2:15][C:16]([OH:19])([CH3:18])[CH3:17])=[C:10]([O:20][CH3:21])[CH:9]=2)[C:4](=[O:22])[CH:3]=1.[F:23][C:24]([F:36])([F:35])[O:25][C:26]1[CH:31]=[CH:30][C:29](B(O)O)=[CH:28][CH:27]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>CN(C=O)C.C(Cl)Cl.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>[OH:19][C:16]([CH3:18])([CH3:17])[CH2:15][O:14][C:11]1[CH:12]=[CH:13][C:8]([N:5]2[CH:6]=[CH:7][C:2]([C:29]3[CH:28]=[CH:27][C:26]([O:25][C:24]([F:23])([F:35])[F:36])=[CH:31][CH:30]=3)=[CH:3][C:4]2=[O:22])=[CH:9][C:10]=1[O:20][CH3:21]

参加物

7

反応物 3

HCID 62657Potassium Phosphate, TribasicHCID 27343864-(Trifluoromethoxy)phenylboronic acidHCID 585802944-chloro-1-(4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenyl)pyridin-2(1H)-one

生成物 1

HCID 469111461-(4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenyl)-4-(4-(trifluoromethoxy)-phenyl)pyridin-2(1H)-one収率 63.6%

試薬・触媒・溶媒 3

HCID 178418397HCID 178418397、化合物触媒HCID 6228Dimethylformamide溶媒HCID 6344Dichloromethane溶媒

反応条件

温度
60 °C

実験手順

A mixture of 4-chloro-1-(4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenyl)pyridin-2(1H)-one Part D (25 mg, 0.08 mmol), 4-(trifluoromethoxy)phenylboronic acid (28 mg, 0.14 mmol), tribasic potassium phosphate (49 mg, 0.23 mmol), and palladium tetrakis (9 mg, 7.7 μmol) in DMF (0.4 mL) was stirred at 60° C. under nitrogen for 17 hours. The reaction mixture was diluted with CH2Cl2, filtered and concentrated. The crude was purified using preparative HPLC (C18 column/10:90:0.1 to 90:10:0.1 MeOH—H2O-TFA). This material further purified by ISCO flash chromatography (silica gel/hexanes-ethyl acetate 100:0 to 0:100 gradient) to afford the title compound 1-(4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenyl)-4-(4-(trifluoromethoxy)-phenyl)pyridin-2(1H)-one B-1 (23.2 mg, 0.049 mmol, 63.6% yield) as a light yellow solid. LC/MS 450 (M+H)+, tR 0.95 min (method 5). 1H NMR (500 MHz, chloroform-d) δ 7.65 (2H, d, J=8.88 Hz), 7.43 (1H, d, J=7.49 Hz), 7.34 (2H, d, J=8.05 Hz), 6.97-7.02 (2H, m), 6.93 (1H, dd), 6.85 (1H, s), 6.48 (1H, dd), 3.89 (3H, s), 3.88 (2H, s), 1.37 (6H, s).

後処理

  1. filtrationfiltered
  2. concentrationconcentrated
  3. customThe crude was purified
  4. customThis material further purified by ISCO flash chromatography (silica gel/hexanes-ethyl acetate 100:0 to 0:100 gradient)

出典と根拠

ORDレコード
ord-d7cb2953bd0c4dd2a56e934683b76812
出典データセット
uspto-grants-2013_10
特許番号
US08563583B2

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