Potassium Carbonate → 2-Amino-7-(4-fluoro-2-(2-fluoropyridin-3-yl)phenyl)-4-methyl-7,8-dihydroquinazolin-5(6H)-one

HRID 1917459ノート

反応式

HRID 1917459 の反応式
[NH2:1][C:2]1[N:11]=[C:10]([CH3:12])[C:9]2[C:8](=[O:13])[CH2:7][CH:6]([C:14]3[CH:19]=[CH:18][C:17]([F:20])=[CH:16][C:15]=3Br)[CH2:5][C:4]=2[N:3]=1.[F:22][C:23]1[C:28](B(O)O)=[CH:27][CH:26]=[CH:25][N:24]=1.C(=O)([O-])[O-].[K+].[K+]>COCCOC>[NH2:1][C:2]1[N:11]=[C:10]([CH3:12])[C:9]2[C:8](=[O:13])[CH2:7][CH:6]([C:14]3[CH:19]=[CH:18][C:17]([F:20])=[CH:16][C:15]=3[C:28]3[C:23]([F:22])=[N:24][CH:25]=[CH:26][CH:27]=3)[CH2:5][C:4]=2[N:3]=1

参加物

5

反応物 3

HCID 11430Potassium CarbonateHCID 27832702-Fluoropyridine-3-boronic acidHCID 57999028HCID 57999028、化合物

生成物 1

HCID 579989472-Amino-7-(4-fluoro-2-(2-fluoropyridin-3-yl)phenyl)-4-methyl-7,8-dihydroquinazolin-5(6H)-one収率 96%

試薬・触媒・溶媒 1

HCID 80711,2-Dimethoxyethane溶媒

実験手順

To a 10 mL recovery flask was added 2-amino-7-(2-bromo-4-fluorophenyl)-4-methyl-7,8-dihydroquinazolin-5(6H)-one (33 mg, 0.0942 mmol, 1.0 eq.), 2-fluoropyridine-3-boronic acid (27 mg, 0.188 mmol, 2.0 eq.), DME (2 mL), potassium carbonate (2.0M aq., 94 μL, 0.188 mmol, 2.0 eq.), and palladium tetrakis triphenylphosphine (5 mg, 0.00471 mmol, 0.05 eq.). The reaction was refluxed overnight whereupon LC/MS analysis judged the reaction to be complete. The reaction mixture was filtered through Celite and concentrated to a residue. The residue was purified via preparatory-HPLC to give the product white solid (30 mg, 96%). 1H NMR (400 MHz, DMSO-d6) δ ppm 2.67 (dd, J=3.54, 1.77 Hz, 1H) 2.89 (br. s., 1H) 3.06 (t, J=12.51 Hz, 2H) 3.18 (br. s., 1H) 7.18 (dd, J=9.60, 2.78 Hz, 1H) 7.31-7.53 (m, 4H) 7.72 (dd, J=8.84, 5.81 Hz, 1H) 7.98 (ddd, J=9.79, 7.52, 1.89 Hz, 1H) 8.28 (d, J=4.80 Hz, 1H). ESI-MS: m/z 367.3 (M+H)+. ESI-MS: m/z 367.3 (M+H)+.

後処理

  1. temperatureThe reaction was refluxed overnight whereupon LC/MS analysis
  2. customthe reaction
  3. filtrationThe reaction mixture was filtered through Celite
  4. concentrationconcentrated to a residue
  5. customThe residue was purified via preparatory-HPLC

出典と根拠

ORDレコード
ord-0d859feaaf394b7098d5a6f03362371a
出典データセット
uspto-grants-2013_12
特許番号
US08618290B2

反応ノート

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