Water → 6-(4-{[Tert-butyl(dimethyl)silyl]oxy}piperidin-1-yl)-2-chloro-N-[(1S)-1-(5-fluoro pyridin-2-yl)ethyl]pyrimidin-4-amine

HRID 573987Notes

Reaction equation

HRID 573987 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([NH:8][C@H:9]([C:11]2[CH:16]=[CH:15][C:14]([F:17])=[CH:13][N:12]=2)[CH3:10])[CH:5]=[C:4](Cl)[N:3]=1.[Si:19]([O:26][CH:27]1[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]1)([C:22]([CH3:25])([CH3:24])[CH3:23])([CH3:21])[CH3:20].C(=O)([O-])[O-].[Cs+].[Cs+].O>CN(C=O)C>[Si:19]([O:26][CH:27]1[CH2:28][CH2:29][N:30]([C:4]2[N:3]=[C:2]([Cl:1])[N:7]=[C:6]([NH:8][C@H:9]([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][N:12]=3)[CH3:10])[CH:5]=2)[CH2:31][CH2:32]1)([C:22]([CH3:25])([CH3:24])[CH3:23])([CH3:21])[CH3:20]

Participants

6

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 114813284-((Tert-butyldimethylsilyl)oxy)piperidineHCID 877597432,6-Dichloro-N-[(1S)-1-(5-fluoropyridin-2-yl)ethyl]pyrimidin-4-amine

Product 1

HCID 894003606-(4-{[Tert-butyl(dimethyl)silyl]oxy}piperidin-1-yl)-2-chloro-N-[(1S)-1-(5-fluoro pyridin-2-yl)ethyl]pyrimidin-4-amineYield 50%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
130 °C

Procedure

A mixture of 2,6-dichloro-N-[(1S)-1-(5-fluoropyridin-2-yl)ethyl]pyrimidin-4-amine (Preparation 10a, 0.66 g, 2.31 mmol), 4-(tert-butyl-dimethylsilanyloxy)piperidine (prepared as described in WO2004/006926, 0.60 g, 2.77 mmol) and cesium carbonate (1.13 g, 3.46 mmol) in N,N′-dimethylformamide (15 mL) was stirred and heated to 130° C. in a sealed tube for 2 hours. After cooling to ambient temperature, water was added and the resulting mixture was extracted with ethyl acetate (×3). The combined organic extract was washed with water and brine, dried (MgSO4), filtered and the solvent was evaporated under reduced pressure. The residue was purified by flash chromatography (hexanes to 6:4 hexanes/ethyl acetate) to give the title compound (0.53 g, 50%) as a white solid.

Workup

  1. temperatureAfter cooling to ambient temperature
  2. extractionthe resulting mixture was extracted with ethyl acetate (×3)
  3. extractionThe combined organic extract
  4. washwas washed with water and brine
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. customthe solvent was evaporated under reduced pressure
  8. customThe residue was purified by flash chromatography (hexanes to 6:4 hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-d854134f9fc04fb797e8637ff5624b82
Source dataset
uspto-grants-2015_05
Patent number
US09034311B2

Reaction notes

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