2-Bromo-1,1-difluoroethane → HCID 59258962, compound

HRID 472245Notes

Reaction equation

HRID 472245 reaction equation
[NH2:1][C:2]1[N:3]=[C:4]([CH3:27])[C:5]2[CH:11]=[C:10]([C:12]3[CH:13]=[N:14][C:15]([O:18][CH3:19])=[CH:16][CH:17]=3)[CH2:9][N:8]([CH:20]3[CH2:25][CH2:24][CH:23]([OH:26])[CH2:22][CH2:21]3)[C:6]=2[N:7]=1.CC(C)([O-:31])C.[K+].Br[CH2:35][CH:36]([F:38])[F:37]>CC(N(C)C)=O.C1COCC1.CS(C)=O>[F:37][CH:36]([F:38])[CH2:35][NH:1][C:2]1[N:3]=[C:4]([CH3:27])[C:5]2[CH:11]=[C:10]([C:12]3[CH:13]=[N:14][C:15]([O:18][CH3:19])=[CH:16][CH:17]=3)[C:9](=[O:31])[N:8]([CH:20]3[CH2:25][CH2:24][CH:23]([OH:26])[CH2:22][CH2:21]3)[C:6]=2[N:7]=1

Participants

7

Reactant 3

HCID 1361862-Bromo-1,1-difluoroethane4×HCID 23665647Potassium tert-butoxide4×HCID 86619625HCID 86619625, compound

Product 1

HCID 59258962HCID 59258962, compound

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolventHCID 8028TetrahydrofuranSolvent4×HCID 31374DimethylacetamideSolvent

Procedure

To a solution of 2-amino-8-(4-hydroxycyclohexyl)-6-(6-methoxypyridin-3-yl)-4-methylpyrido[2,3-d]pyrimidin-[7(8H)-one (50 mg, 0.13 mmol) in anhydrous DMA (1.0 ml) at room temperature was added a 1M solution of potassium tert-butoxide in THF (0.14 ml). After stirring at R.T. for 1 hour, to the reaction mixture was added 1-bromo-2,2-difluoroethane (20.9 mg, 0.14 mmol). After stirring at room temperature for 16 h and 4.5 h at 80° C. the reaction mixture was cooled to room temperature, and 1M solution of potassium tert-butoxide in THF (0.16 ml) and 1-bromo-2,2-difluoroethane (41.8 mg, 0.28 mmol) were added. After stirring at 80° C. for 16 h, to the reaction mixture was added another 1M solution of potassium tert-butoxide in THF (0.1 ml) and 1-bromo-2,2-difluoroethane (62.7 mg, 0.42 mmol). After stirring at 80° C. for 16 h, to the reaction mixture another 3 eq of 1M solution of potassium tert-butoxide in THF and 3 eq of 1-bromo-2,2-difluoroethane were added. After heating in microwave for 20 mins at 120° C., the reaction mixture was cooled to room temperature and diluted with DMSO, the precipitate was removed by filtration. The filtrate was combined and purified using reversed phase column eluted with acetonitrile (0.1% acetic acid) and water (0.1% acetic acid) to give the titled compound as a solid weighted 14.6 mg.

Workup

  1. stirringAfter stirring at room temperature for 16 h and 4.5 h at 80° C. the reaction mixture
  2. temperaturewas cooled to room temperature
  3. stirringAfter stirring at 80° C. for 16 h, to the reaction mixture
  4. additionwere added
  5. temperatureAfter heating in microwave for 20 mins at 120° C.
  6. temperaturethe reaction mixture was cooled to room temperature
  7. customthe precipitate was removed by filtration
  8. custompurified
  9. washeluted with acetonitrile (0.1% acetic acid) and water (0.1% acetic acid)

Sources & evidence

ORD record
ord-7f41f5aec10540b2bd5e7b9eb2293e3e
Source dataset
uspto-grants-2014_01
Patent number
US08633204B2

Reaction notes

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