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

HRID 2042080Notes

Reaction equation

HRID 2042080 reaction equation
[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[CH:36]=[C:37]([OH:42])[CH:38]=[CH:39][C:40]=1[F:41].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:42][C:37]4[CH:38]=[CH:39][C:40]([F:41])=[C:35]([NH2:34])[CH:36]=4)[N:14]=3)[CH:10]=[N:9]2)=[CH:5][CH:4]=1

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 70297m-Chloroperbenzoic acidHCID 135191803-Amino-4-fluorophenolHCID 672523404-(1-(4-methoxybenzyl)-1H-pyrazol-4-yl)-2-(methylthio)pyrimidine

Product 1

HCID 672528535-(4-(1-(4-methoxybenzyl)-1H-pyrazol-4-yl)pyrimidin-2-yloxy)-2-fluorobenzenamineYield 84%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 4-(1-(4-methoxybenzyl)-1H-pyrazol-4-yl)-2-(methylthio)pyrimidine (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 3-amino-4-fluorophenol (165 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-fluorobenzenamine (210 mg, 84% yield). 1H NMR (300 MHz, DMSO-d6) δ 8.50 (s, 1H), 8.44, (d, J=5.4 Hz, 1H), 8.10 (s, 1H), 7.42 (d, J=5.4 Hz, 1H), 7.25 (d, J=8.4 Hz, 2H), 6.98 (t, J=9.6 Hz, 1H), 6.91 (d, J=8.4 Hz, 2H), 6.52 (dd, J=2.7, 8.7 Hz, 1H), 6.28 (m, 1H), 5.30 (br s, 2H), 5.26 (s, 2H), 3.72 (s, 3H); MS (ESI) m/z: 392.2 (M+H+).

Workup

  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

Sources & evidence

ORD record
ord-bcb85544b8dc470f91f332b13fe08b5a
Source dataset
uspto-grants-2013_11
Patent number
US08586565B2

Reaction notes

Loading…