4-(2,2-Difluoropropoxyl)pyrimidine-5-carbonitrile → C-[4-(2,2-Difluoro-propoxy)-pyrimidin-5-yl]-methylamine

HRID 1749445Notes

Reaction equation

HRID 1749445 reaction equation
[F:1][C:2]([F:14])([CH3:13])[CH2:3][O:4][C:5]1[C:10]([C:11]#[N:12])=[CH:9][N:8]=[CH:7][N:6]=1>C1COCC1.[Ni]>[F:14][C:2]([F:1])([CH3:13])[CH2:3][O:4][C:5]1[C:10]([CH2:11][NH2:12])=[CH:9][N:8]=[CH:7][N:6]=1

Participants

4

Reactant 1

HCID 1181620714-(2,2-Difluoropropoxyl)pyrimidine-5-carbonitrile

Product 1

HCID 118162151C-[4-(2,2-Difluoro-propoxy)-pyrimidin-5-yl]-methylamineYield 30%

Reagents, catalysts & solvents 2

HCID 935NickelCatalystHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 4-(2,2-difluoropropoxyl)pyrimidine-5-carbonitrile (850 mg, 4.27 mmol) in THF (30 mL) was added Raney-nickel (600 mg). The mixture was de-gassed under vacuum for 10 minutes, and then hydrogenated under a fully-inflated balloon at room temperature overnight. The mixture was filtered through a pad of Celite and the cake was washed with ethyl acetate (200 mL). The filtrate was removed under vacuum and the residue was purified by preparative HPLC (5% to 60% acetonitrile in water) to give the product (260 mg, 1.28 mmol, 30% yield) as a yellow oil. MS (ESI) m/z 204.0 [M+H]+.

Workup

  1. customThe mixture was de-gassed under vacuum for 10 minutes
  2. filtrationThe mixture was filtered through a pad of Celite
  3. washthe cake was washed with ethyl acetate (200 mL)
  4. customThe filtrate was removed under vacuum
  5. customthe residue was purified by preparative HPLC (5% to 60% acetonitrile in water)

Sources & evidence

ORD record
ord-2e0ea394790e4b408908932fa27e26db
Source dataset
uspto-grants-2015_10
Patent number
US09156798B2

Reaction notes

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