Diethyl Ether → 4-Chloro-N-(6-methoxypyridin-3-yl)-5-(trifluoromethyl)pyrimidin-2-amine

HRID 592471Notes

Reaction equation

HRID 592471 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.[NH2:18][C:19]1[CH:20]=[CH:21][C:22]([O:25][CH3:26])=[N:23][CH:24]=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:18][C:19]2[CH:24]=[N:23][C:22]([O:25][CH3:26])=[CH:21][CH:20]=2)[N:12]=1

Participants

8

Reactant 4

HCID 3283Diethyl EtherHCID 8471TriethylamineHCID 811216-Methoxy-3-pyridinylamineHCID 27827742,4-Dichloro-5-(trifluoromethyl)pyrimidine

Product 1

HCID 867123404-Chloro-N-(6-methoxypyridin-3-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). The mixture was stirred for 10 minutes and then diluted with t-BuOH (25 mL) and DCE (25 mL) before 5-amino-2-methoxypyridine (629 mg, 5.07 mmol) and Et3N (1.93 mL, 13.8 mmol) were added. The mixture was stirred at room temperature overnight and the volatiles were removed in vacuo. The resultant residue was suspended in water (250 mL) and sonicated for 10 minutes before the solid was isolated by vacuum filtration. The filter cake was washed with water and air dried and then dissolved in DCM and adsorbed onto silica gel. Purification by column chromatography (Biotage Isolera, 40 g SiO2 cartridge, 0-100% EtOAc in petroleum benzine 40-60° C.) gave the title compound A68 as a white solid (944 mg, 67%). LCMS-A: rt 6.62 min; m/z 305 [M+H]+.

Workup

  1. additionwere added
  2. stirringThe mixture was stirred at room temperature overnight
  3. customthe volatiles were removed in vacuo
  4. customsonicated for 10 minutes before the solid
  5. customwas isolated by vacuum filtration
  6. washThe filter cake was washed with water and air
  7. customdried
  8. dissolutiondissolved in DCM
  9. customPurification by column chromatography (Biotage Isolera, 40 g SiO2 cartridge, 0-100% EtOAc in petroleum benzine 40-60° C.)

Sources & evidence

ORD record
ord-c6707c4b85e541d4856622a6374f7bcb
Source dataset
uspto-grants-2016_01
Patent number
US09238644B2

Reaction notes

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