Potassium Carbonate → 5-(4-(1-(4-methoxybenzyl)-1H-pyrazol-4-yl)pyrimidin-2-yloxy)-2-fluoro-4-methylbenzenamine

HRID 2060716노트

반응식

HRID 2060716 반응식
[CH3:1][O:2][C:3]1[CH:22]=[CH:21][C:6]([CH2:7][N:8]2[CH:12]=[C:11]([C:13]3[CH:18]=[CH:17][N:16]=[C:15](SC)[N:14]=3)[CH:10]=[N:9]2)=[CH:5][CH:4]=1.C1C=C(Cl)C=C(C(OO)=O)C=1.[NH2:34][C:35]1[C:36]([F:43])=[CH:37][C:38]([CH3:42])=[C:39]([OH:41])[CH:40]=1.C([O-])([O-])=O.[K+].[K+]>ClCCl.CN(C=O)C.O>[CH3:1][O:2][C:3]1[CH:22]=[CH:21][C:6]([CH2:7][N:8]2[CH:12]=[C:11]([C:13]3[CH:18]=[CH:17][N:16]=[C:15]([O:41][C:39]4[C:38]([CH3:42])=[CH:37][C:36]([F:43])=[C:35]([NH2:34])[CH:40]=4)[N:14]=3)[CH:10]=[N:9]2)=[CH:5][CH:4]=1

참가 물질

8

반응물 4

HCID 11430Potassium CarbonateHCID 70297m-Chloroperbenzoic acidHCID 101540985-Amino-4-fluoro-2-methylphenolHCID 672523404-(1-(4-methoxybenzyl)-1H-pyrazol-4-yl)-2-(methylthio)pyrimidine

생성물 1

HCID 673975355-(4-(1-(4-methoxybenzyl)-1H-pyrazol-4-yl)pyrimidin-2-yloxy)-2-fluoro-4-methylbenzenamine수율 84%

시약·촉매·용매 3

HCID 962Water용매HCID 6228Dimethylformamide용매HCID 6344Dichloromethane용매

실험 절차

To a solution of 4-(1-(4-methoxybenzyl)-1H-pyrazol-4-yl)-2-(methylthio)pyrimidine from Example A18 (200 mg, 0.64 mmol) in dichloromethane was added m-CPBA (220 mg, 1.28 mmol). The reaction was stirred for 2 hour at RT. Water was added, the organic layer was separated and the aqueous layer was extracted with dichloromethane. The combined organics were washed with brine and concentrated in vacuo. The residue was combined with 5-amino-4-fluoro-2-methylphenol (180 mg, 1.28 mmol) and K2CO3 (176 mg, 1.28 mmol) in DMF (5 mL) and the resultant mixture was heated at 90° C. overnight. After filtration and concentration, the residue was purified by silica gel column chromatography to give 5-(4-(1-(4-methoxybenzyl)-1H-pyrazol-4-yl)pyrimidin-2-yloxy)-2-fluoro-4-methylbenzenamine (210 mg, 84% yield). MS (ESI) m/z: 406.2 (M+H+).

후처리

  1. customthe organic layer was separated
  2. extractionthe aqueous layer was extracted with dichloromethane
  3. washThe combined organics were washed with brine
  4. concentrationconcentrated in vacuo
  5. filtrationAfter filtration and concentration
  6. customthe residue was purified by silica gel column chromatography

출처 및 근거

ORD 기록
ord-bca64a492d124317adfcad19c0573107
출처 데이터셋
uspto-grants-2012_10
특허 번호
US08278331B2

반응 노트

불러오는 중…