Dichloromethane → 4-[1-(2,2-Difluoroethyl)-3-iodo-1H-pyrazol-4-yl]-2-(methylthio)pyrimidine

HRID 500733Notes

Reaction equation

HRID 500733 reaction equation
[I:1][C:2]1[NH:6][N:5]=[CH:4][C:3]=1[C:7]1[CH:12]=[CH:11][N:10]=[C:9]([S:13][CH3:14])[N:8]=1.C([O-])([O-])=O.[K+].[K+].[F:21][CH:22]([F:25])[CH2:23]I.C(Cl)Cl>CN(C=O)C.CO>[F:21][CH:22]([F:25])[CH2:23][N:5]1[CH:4]=[C:3]([C:7]2[CH:12]=[CH:11][N:10]=[C:9]([S:13][CH3:14])[N:8]=2)[C:2]([I:1])=[N:6]1

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 38335651,1-Difluoro-2-iodoethaneHCID 468641604-(5-Iodo-1H-pyrazol-4-yl)-2-(methylsulfanyl)pyrimidine

Product 1

HCID 578563034-[1-(2,2-Difluoroethyl)-3-iodo-1H-pyrazol-4-yl]-2-(methylthio)pyrimidine

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of Intermediate A (83 g, 0.26 mol) in DMF (600 mL) were K2CO3 (58 g, 0.417 mol) and 1,1-difluoro-2-iodo-ethane (60 g, 0.313 mol). Then the mixture was stirred at room temperature overnight. TLC (CH2Cl2: MeOH=20:1) showed the reaction was complete. The mixture was concentrated and the solid was diluted with CH2Cl2 (500 mL). The slurry was filtered and the filtrate was concentrated to give crude product, which was purified via prep. SFC to give compound B-33-1 (41.1 g, 41.3%) as a white solid.

Workup

  1. concentrationThe mixture was concentrated
  2. additionthe solid was diluted with CH2Cl2 (500 mL)
  3. filtrationThe slurry was filtered
  4. concentrationthe filtrate was concentrated
  5. customto give crude product, which
  6. customwas purified via prep
  7. customSFC to give compound B-33-1 (41.1 g, 41.3%) as a white solid

Sources & evidence

ORD record
ord-9295e04992444ecf89f3017e5d1f211e
Source dataset
uspto-grants-2010_08
Patent number
US07772246B2

Reaction notes

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