2-Methyl-2H-pyrazol-3-ylamine → HCID 86696706, compound

HRID 1774206Notes

Reaction equation

HRID 1774206 reaction equation
[O:1]([CH2:9][C@@H:10]([N:19]1[CH:24]=[CH:23][C:22]([C:25]2[CH:30]=[CH:29][N:28]=[C:27](S(C)(=O)=O)[N:26]=2)=[CH:21][C:20]1=[O:35])[C:11]1[CH:16]=[CH:15][C:14]([Cl:17])=[C:13]([F:18])[CH:12]=1)[Si:2]([C:5]([CH3:8])([CH3:7])[CH3:6])([CH3:4])[CH3:3].[CH3:36][N:37]1[C:41]([NH2:42])=[CH:40][CH:39]=[N:38]1>CN(C=O)C>[Si:2]([O:1][CH2:9][C@@H:10]([N:19]1[CH:24]=[CH:23][C:22]([C:25]2[CH:30]=[CH:29][N:28]=[C:27]([NH:42][C:41]3[N:37]([CH3:36])[N:38]=[CH:39][CH:40]=3)[N:26]=2)=[CH:21][C:20]1=[O:35])[C:11]1[CH:16]=[CH:15][C:14]([Cl:17])=[C:13]([F:18])[CH:12]=1)([C:5]([CH3:8])([CH3:7])[CH3:6])([CH3:4])[CH3:3]

Participants

4

Reactant 2

HCID 1369272-Methyl-2H-pyrazol-3-ylamineHCID 71727006HCID 71727006, compound

Product 1

HCID 86696706HCID 86696706, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

(S)-1-(2-(tert-Butyldimethylsiloxy)-1-(4-chloro-3-fluorophenyl)ethyl)-4-(2-(methylsulfonyl)pyrimidin-4-yl)pyridine-2(1H)-one (47 mg, 0.087 mmol), 2-methyl pyrazole-3-amine (0.175 mmol, 2.0 equivalents) and anhydrous DMF (3.0 mL) were added to a 25 mL round bottomed flask equipped with a stirring bar. The flask was capped with a rubber septum and flushed with nitrogen. Under a blanket of nitrogen, sodium hydride (8.5 mg, 60% dispersion in mineral oil) was added in one portion. The flask was flushed with nitrogen, capped and stirred at room temperature. The reaction progress was monitored by LCMS, and after 30 minutes, the starting material was consumed. The reaction mixture was quenched by the addition of water (0.5 mL) and ethyl acetate (15 mL) The contents of the round bottomed flask were transferred to a 125 mL separatory funnel, and the reaction flask was rinsed several times with additional ethyl acetate. Crude (S)-1-(2-((tert-butyldimethylsilyl)oxy)-1-(4-chloro-3-fluorophenyl)ethyl)-4-(2-((1-methyl-1H-pyrazol-5-yl)amino)pyrimidin-4-yl)pyridin-2(1H)-one was partitioned between ethyl acetate and water (80 mL/30 mL). The ethyl acetate layer was washed once with brine, dried (MgSO4), filtered and concentrated to give crude (S)-1-(2-((tert-butyldimethylsilyl)oxy)-1-(4-chloro-3-fluorophenyl)ethyl)-4-(2-((1-methyl-1H-pyrazol-5-yl)amino)pyrimidin-4-yl)pyridin-2(1H)-one. The crude was taken directly into the deprotection step.

Workup

  1. customequipped with a stirring bar
  2. customThe flask was capped with a rubber septum
  3. customflushed with nitrogen
  4. additionUnder a blanket of nitrogen, sodium hydride (8.5 mg, 60% dispersion in mineral oil) was added in one portion
  5. customThe flask was flushed with nitrogen
  6. customcapped
  7. customthe starting material was consumed
  8. customThe reaction mixture was quenched by the addition of water (0.5 mL) and ethyl acetate (15 mL) The contents of the round bottomed flask
  9. customwere transferred to a 125 mL separatory funnel
  10. washthe reaction flask was rinsed several times with additional ethyl acetate
  11. customCrude (S)-1-(2-((tert-butyldimethylsilyl)oxy)-1-(4-chloro-3-fluorophenyl)ethyl)-4-(2-((1-methyl-1H-pyrazol-5-yl)amino)pyrimidin-4-yl)pyridin-2(1H)-one was partitioned between ethyl acetate and water (80 mL/30 mL)
  12. washThe ethyl acetate layer was washed once with brine
  13. dry with materialdried (MgSO4)
  14. filtrationfiltered
  15. concentrationconcentrated

Sources & evidence

ORD record
ord-3080a318accc498e9fe27e5c4722eb64
Source dataset
uspto-grants-2016_02
Patent number
US09259470B2

Reaction notes

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