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

HRID 1917459노트

반응식

HRID 1917459 반응식
[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

참가 물질

5

반응물 3

HCID 11430Potassium CarbonateHCID 27832702-Fluoropyridine-3-boronic acidHCID 57999028HCID 57999028, 화합물

생성물 1

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

시약·촉매·용매 1

HCID 80711,2-Dimethoxyethane용매

실험 절차

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)+.

후처리

  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

출처 및 근거

ORD 기록
ord-0d859feaaf394b7098d5a6f03362371a
출처 데이터셋
uspto-grants-2013_12
특허 번호
US08618290B2

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