Sodium hydride → 2-methyl-6-(2-{(1S,2R)-2-[1-(5-methylpyrimidin-2-yl)piperidin-4-yl]cyclopropyl}ethoxy)pyrimidine-4-carbonitrile

HRID 1798838Notes

Reaction equation

HRID 1798838 reaction equation
[H-].[Na+].[CH3:3][C:4]1[CH:5]=[N:6][C:7]([N:10]2[CH2:15][CH2:14][CH:13]([C@H:16]3[CH2:18][C@H:17]3[CH2:19][CH2:20][OH:21])[CH2:12][CH2:11]2)=[N:8][CH:9]=1.Cl[C:23]1[N:28]=[C:27]([CH3:29])[N:26]=[C:25]([C:30]#[N:31])[CH:24]=1>CN(C=O)C.CCOC(C)=O.O>[CH3:29][C:27]1[N:26]=[C:25]([C:30]#[N:31])[CH:24]=[C:23]([O:21][CH2:20][CH2:19][C@@H:17]2[CH2:18][C@@H:16]2[CH:13]2[CH2:12][CH2:11][N:10]([C:7]3[N:8]=[CH:9][C:4]([CH3:3])=[CH:5][N:6]=3)[CH2:15][CH2:14]2)[N:28]=1

Participants

7

Reactant 3

HCID 24758Sodium hydrideHCID 581284976-Chloro-2-methylpyrimidine-4-carbonitrileHCID 581285982-{(1S,2R)-2-[1-(5-methylpyrimidin-2-yl)piperidin-4-yl]cyclopropyl}ethanol

Product 1

HCID 444677582-methyl-6-(2-{(1S,2R)-2-[1-(5-methylpyrimidin-2-yl)piperidin-4-yl]cyclopropyl}ethoxy)pyrimidine-4-carbonitrile

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

NaH (60%, 18 mg, 0.45 mmol, 1.2 eq) was placed in a 1 dram vial and DMF (1.2 mL) added. A solution of 2-{(1S,2R)-2-[1-(5-methylpyrimidin-2-yl)piperidin-4-yl]cyclopropyl}ethanol (100 mg, 0.375 mmol) was added dropwise (0.5 mL) to the slurry, and the mixture stirred at RT for 10 min. The solution was cooled to −20° C., and a solution of 6-chloro-2-methylpyrimidine-4-carbonitrile (115 mg, 0.75 mmol) in DMF (0.5 mL) was added drop-wise. The red mixture was stirred for 40 minutes. A solution of ice-cold saturated NH4Cl (aq., 1 mL) was added, and the mixture diluted with EtOAc (100 mL) and water (50 mL). The mixture was transferred to a separatory funnel, the mixture shaken, and the layers separated. The organic fraction was washed with water (20 mL), dried over MgSO4, filtered, and concentrated in vac. The red oil was purified by chromatography on silica gel 1:7 EtOAc:Hexanes to give the title compound.

Workup

  1. temperatureThe solution was cooled to −20° C.
  2. stirringThe red mixture was stirred for 40 minutes
  3. customThe mixture was transferred to a separatory funnel
  4. stirringthe mixture shaken
  5. customthe layers separated
  6. washThe organic fraction was washed with water (20 mL)
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated in vac
  10. customThe red oil was purified by chromatography on silica gel 1:7 EtOAc

Sources & evidence

ORD record
ord-911db5a6fe6d44bdad07e0e550a1b83d
Source dataset
uspto-grants-2013_01
Patent number
US08343990B2

Reaction notes

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