Diethyl Ether → 4-Chloro-N-(1-methyl-1H-pyrazol-4-yl)-5-(trifluoromethyl)pyrimidin-2-amine

HRID 592463Notes

Reaction equation

HRID 592463 reaction equation
CCOCC.Cl[C:7]1[N:12]=[C:11]([Cl:13])[C:10]([C:14]([F:17])([F:16])[F:15])=[CH:9][N:8]=1.[CH3:18][N:19]1[CH:23]=[C:22]([NH2:24])[CH:21]=[N:20]1.CCN(CC)CC>CC(O)(C)C.ClCCCl.[Cl-].[Cl-].[Zn+2]>[Cl:13][C:11]1[C:10]([C:14]([F:17])([F:16])[F:15])=[CH:9][N:8]=[C:7]([NH:24][C:22]2[CH:21]=[N:20][N:19]([CH3:18])[CH:23]=2)[N:12]=1

Participants

8

Reactant 4

HCID 3283Diethyl EtherHCID 8471TriethylamineHCID 27827742,4-Dichloro-5-(trifluoromethyl)pyrimidineHCID 47709901-methyl-1H-pyrazol-4-amine

Product 1

HCID 867123374-Chloro-N-(1-methyl-1H-pyrazol-4-yl)-5-(trifluoromethyl)pyrimidin-2-amine

Reagents, catalysts & solvents 3

HCID 3007855ZincchlorideCatalystHCID 111,2-DichloroethaneSolvent2×HCID 6386tert-ButanolSolvent2×

Procedure

A 1.0 M solution of ZnCl2 in Et2O (5.07 mL, 5.07 mmol) was added to a solution of 2,4-dichloro-5-(trifluoromethyl)pyrimidine (1.00 g, 4.61 mmol) in t-BuOH (25 mL) and DCE (25 mL) and the mixture was stirred for 10 minutes. The mixture was diluted with t-BuOH (25 mL) and DCE (25 mL) before 1-methyl-1H-pyrazol-4-amine (492 mg, 5.07 mmol) and Et3N (1.93 mL, 13.83 mmol) were added and stirring was continued at room temperature overnight. The volatiles were removed in vacuo and the resultant residue suspended in water (250 mL) and sonicated for 10 minutes. The solid was collected by vacuum filtration and the filter cake washed with water and then air dried. The solid was dissolved in DCM, adsorbed onto silica gel and purified by column chromatography (Biotage Isolera, 40 g SiO2 cartridge, 0-100% EtOAc in petroleum benzine 40-60° C.) to give the title compound A64 as a white solid (182 mg, 14%). LCMS-A: rt 6.113 min; m/z 278.1 [M+H]+.

Workup

  1. additionwere added
  2. stirringstirring
  3. waitwas continued at room temperature overnight
  4. customThe volatiles were removed in vacuo
  5. customsonicated for 10 minutes
  6. filtrationThe solid was collected by vacuum filtration
  7. washthe filter cake washed with water
  8. customair dried
  9. dissolutionThe solid was dissolved in DCM
  10. custompurified by column chromatography (Biotage Isolera, 40 g SiO2 cartridge, 0-100% EtOAc in petroleum benzine 40-60° C.)

Sources & evidence

ORD record
ord-4ad3fa111cc5400e88e024ac443860b0
Source dataset
uspto-grants-2016_01
Patent number
US09238644B2

Reaction notes

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