Water → 4-(2-Difluoromethoxypyridin-4-Yloxy)-2-(Pyrazin-2-yl)-Pyrimidine

HRID 651733Notes

Reaction equation

HRID 651733 reaction equation
O.Cl[C:3](Cl)(Cl)[CH2:4][CH:5](Cl)OCC.Cl.[N:13]1[CH:18]=[CH:17][N:16]=[CH:15][C:14]=1[C:19]([NH2:21])=[NH:20].[F:22][CH:23]([F:32])[O:24][C:25]1[CH:30]=[C:29]([OH:31])[CH:28]=[CH:27][N:26]=1.C(=O)([O-])[O-].[K+].[K+].ClC(Cl)=CC=O>C(COC)OC.Cl.N1C=CN=CC=1C(N)=N>[F:32][CH:23]([F:22])[O:24][C:25]1[CH:30]=[C:29]([O:31][C:3]2[CH:4]=[CH:5][N:21]=[C:19]([C:14]3[CH:15]=[N:16][CH:17]=[CH:18][N:13]=3)[N:20]=2)[CH:28]=[CH:27][N:26]=1

Participants

9

Reactant 6

HCID 962WaterHCID 11430Potassium CarbonateHCID 175543,3-Dichloro-2-propenalHCID 470895Pyrazine-2-carboxamidine hydrochlorideHCID 123508221,1,1,3-Tetrachloro-3-ethoxypropaneHCID 178516524HCID 178516524, compound

Product 1

HCID 97970114-(2-Difluoromethoxypyridin-4-Yloxy)-2-(Pyrazin-2-yl)-PyrimidineYield 82%

Reagents, catalysts & solvents 2

HCID 470895Pyrazine-2-carboxamidine hydrochlorideCatalystHCID 80711,2-DimethoxyethaneSolvent2×

Conditions

Temperature
60 °C

Procedure

Water (20 mmoles) is added to a solution of 1,1,1,3-tetrachloro-3-ethoxypropane (10 mmoles) in dimethoxyethane (25 ml). The mixture is stirred for 2 h at 60° C. The resulting mixture is slowly added to a mixture consisting of a pyrazine-2-carboxamidine hydrochloride (10 mmoles), 2-difluoromethoxypyridin-4-ol (10 mmoles), potassium carbonate (60 mmoles) and dimethoxyethane (50 ml), which is stirred under reflux. When the addition of 3,3-dichloroacrolein solution is completed additional pyrazine-2-carboxamidine hydrochloride (0.5 mmoles) is added. The reaction mixture is stirred for 2 hours under reflux and subsequently cooled down to ambient temperature, filtered through silica, and the organic phase is concentrated in vacuo. The residue is purified by chromatography on SiO2 (ethyl acetate) to yield 2,60 g (82%) of beige crystals having a melting point of 128-129° C.

Workup

  1. additionThe resulting mixture is slowly added to a mixture
  2. stirringis stirred
  3. temperatureunder reflux
  4. additionis added
  5. stirringThe reaction mixture is stirred for 2 hours
  6. temperatureunder reflux
  7. temperaturesubsequently cooled down to ambient temperature
  8. filtrationfiltered through silica
  9. concentrationthe organic phase is concentrated in vacuo
  10. customThe residue is purified by chromatography on SiO2 (ethyl acetate)

Sources & evidence

ORD record
ord-6a574ee6dba64ceaabfc039473b65c06
Source dataset
uspto-grants-2001_08
Patent number
US06281358B1

Reaction notes

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