Water → HCID 50939794, compound

HRID 1039067Notes

Reaction equation

HRID 1039067 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.Cl[C:21]1[CH:26]=[N:25][C:24]([N:27]2[CH:31]=[N:30][CH:29]=[N:28]2)=[CH:23][N:22]=1.C(=O)([O-])[O-].[K+].[K+].O>CN1C(=O)CCC1.C(O)(=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:21]3[CH:26]=[N:25][C:24]([N:27]4[CH:31]=[N:30][CH:29]=[N:28]4)=[CH:23][N:22]=3)[CH2:10][CH2:9]2)=[N:6][CH:7]=1

Participants

7

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 677784742-{(1S,2S)-2-[1-(5-chloropyrimidin-2-yl)piperidin-4-yl]cyclopropyl}ethanamineHCID 772311952-chloro-5-(1H-1,2,4-triazol-1-yl)pyrazine

Product 1

HCID 50939794HCID 50939794, compound

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
90 °C

Procedure

2-{(1S,2S)-2-[1-(5-chloropyrimidin-2-yl)piperidin-4-yl]cyclopropyl}ethanamine (50 mg, 0.18 mmol) from step 3, Example 5 and 2-chloro-5-(1H-1,2,4-triazol-1-yl)pyrazine (35.6 mg, 0.20 mmol) were added in NMP (0.89 mL), then potassium carbonate (73.8 mg, 0.53 mmol) was added and the reaction was heated to 90° C. overnight. The reaction was cooled to room temperature, water (10 mL) was added and drops of acetic acid were added to adjust pH value to ˜4, extracted with ethyl acetate (20 mL), second wash with brine (10 mL). The water phase was back extracted with ethyl acetate (10 mL×2). The organic phase were combined and dried by magnesium sulfate, filtered and concentrated and purified by column chromatography through a 25 gram Biotage SNAP KP-Sil™ silica gel cartridge eluting with 30% ethyl acetate/hexane to give the title compound as a white solid.

Workup

  1. temperatureThe reaction was cooled to room temperature
  2. extractionextracted with ethyl acetate (20 mL)
  3. washsecond wash with brine (10 mL)
  4. extractionThe water phase was back extracted with ethyl acetate (10 mL×2)
  5. dry with materialdried by magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. custompurified by column chromatography through a 25 gram Biotage SNAP KP-Sil™ silica gel cartridge
  9. washeluting with 30% ethyl acetate/hexane

Sources & evidence

ORD record
ord-7f46a2934ba44b418715b13dff538db7
Source dataset
uspto-grants-2013_10
Patent number
US08552022B2

Reaction notes

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