Dichloromethane → 2-(2,4-Difluorophenyl)-3-(2-methanesulfonylpyrimidin-4-yl)-8-methylimidazo[1,2-a]pyrazine

HRID 2233109Notes

Reaction equation

HRID 2233109 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[N:10]=[C:11]2[C:16]([CH3:17])=[N:15][CH:14]=[CH:13][N:12]2[C:18]=1[C:19]1[CH:24]=[CH:23][N:22]=[C:21](SC)[N:20]=1.O[O:28][S:29]([O-:31])=O.[K+].[CH2:33](Cl)Cl>CO.O>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[N:10]=[C:11]2[C:16]([CH3:17])=[N:15][CH:14]=[CH:13][N:12]2[C:18]=1[C:19]1[CH:24]=[CH:23][N:22]=[C:21]([S:29]([CH3:33])(=[O:31])=[O:28])[N:20]=1

Participants

6

Reactant 3

HCID 6344DichloromethaneHCID 23707502Potassium hydroxy sulfiteHCID 574387732-(2,4-Difluorophenyl)-8-methyl-3-(2-methylsulfanylpyrimidin-4-yl)-imidazo[1,2-a]pyrazine

Product 1

HCID 574387742-(2,4-Difluorophenyl)-3-(2-methanesulfonylpyrimidin-4-yl)-8-methylimidazo[1,2-a]pyrazineYield 28%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent2×

Procedure

To a solution of 2-(2,4-difluorophenyl)-8-methyl-3-(2-methylsulfanylpyrimidin-4-yl)-imidazo[1,2-a]pyrazine (5.26 g, ˜75% pure, 10.7 mmol) in DCM (90 mL) and MeOH (90 mL) was added a solution of Oxone® (13.1 g, 21.4 mmol) in water (45 mL). After about 16 h, the mixture was diluted with water (250 mL) and extracted with DCM (3×200 mL). The combine organic layers were washed with brine (100 mL), dried over MgSO4, filtered, and concentrated. The crude material was purified by silica gel chromatography using a step-wise gradient of DCM:EtOAc (3:1 to 3:2 to 1:1). Fractions enriched in product were crystallized from hot ACN. The resulting solid was filtered, washing with additional ACN, and dried in a vacuum oven at about 70° C. for about 2 h to give 1.19 g (28%) of the title compound. Additional product can be obtained from further purification of column fractions and filtrate: LC/MS (Table 1, Method b) Rt=1.77 min; MS m/z: 402.1 (M+H)+.

Workup

  1. extractionextracted with DCM (3×200 mL)
  2. washThe combine organic layers were washed with brine (100 mL)
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude material was purified by silica gel chromatography
  7. customwere crystallized from hot ACN
  8. filtrationThe resulting solid was filtered
  9. washwashing with additional ACN
  10. customdried in a vacuum oven at about 70° C. for about 2 h

Sources & evidence

ORD record
ord-fe1470f5458e4f3fa437606b4ab2120a
Source dataset
uspto-grants-2010_05
Patent number
US07709468B2

Reaction notes

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