Water → HCID 50939525, compound

HRID 1039055Notes

Reaction equation

HRID 1039055 reaction equation
[Cl:1][C:2]1[CH:3]=[N:4][C:5]([N:8]2[CH2:13][CH2:12][CH:11]([C@H:14]3[CH2:16][C@H:15]3[CH2:17][CH2:18][NH2:19])[CH2:10][CH2:9]2)=[N:6][CH:7]=1.C(=O)([O-])[O-].[Cs+].[Cs+].Cl[C:27]1[N:32]=[C:31]([CH3:33])[N:30]=[C:29]([C:34]#[N:35])[CH:28]=1.O>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[N:4][C:5]([N:8]2[CH2:13][CH2:12][CH:11]([C@H:14]3[CH2:16][C@H:15]3[CH2:17][CH2:18][NH:19][C:27]3[N:32]=[C:31]([CH3:33])[N:30]=[C:29]([C:34]#[N:35])[CH:28]=3)[CH2:10][CH2:9]2)=[N:6][CH:7]=1

Participants

6

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 581284976-Chloro-2-methylpyrimidine-4-carbonitrileHCID 677784742-{(1S,2S)-2-[1-(5-chloropyrimidin-2-yl)piperidin-4-yl]cyclopropyl}ethanamine

Product 1

HCID 50939525HCID 50939525, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

2-{(1S,2S)-2-[1-(5-chloropyrimidin-2-yl)piperidin-4-yl]cyclopropyl}ethanamine (29 mg, 0.10 mmol) from step 3 of this example was dissolved in DMF (0.4 mL), cesium carbonate (168 mg, 0.52 mmol) was added, stirred at room temperature for 10 minutes, then cooled down to 0° C. 6-chloro-2-methylpyrimidine-4-carbonitrile (17.5 mg, 0.114 mmol; from step 4 of this example) was added in DMF (0.1 mL) via syringe. Reaction was kept at 0° C. for 30 minutes, then warmed up to room temperature for 1 hour. Water (50 mL) was added, extracted with EtOAc (50 mL×2), second wash with Brine (20 mL). The combined organic phase was dried by magnesium sulfate, filter, concentrated and purified by column chromatography through a 40 gram RediSep Rf™ silica gel cartridge eluting with 17% acetone/hexanes to give the title compound as a pale yellow solid.

Workup

  1. temperaturecooled down to 0° C
  2. customReaction
  3. waitwas kept at 0° C. for 30 minutes
  4. temperaturewarmed up to room temperature for 1 hour
  5. extractionextracted with EtOAc (50 mL×2)
  6. washsecond wash with Brine (20 mL)
  7. dry with materialThe combined organic phase was dried by magnesium sulfate
  8. filtrationfilter
  9. concentrationconcentrated
  10. custompurified by column chromatography through a 40 gram RediSep Rf™ silica gel cartridge
  11. washeluting with 17% acetone/hexanes

Sources & evidence

ORD record
ord-24d3a710626d411bb8cbdb4f3c556adb
Source dataset
uspto-grants-2013_10
Patent number
US08552022B2

Reaction notes

Loading…