Water → N-(2-{(1S,2S)-2-[1-(5-chloropyrimidin-2-yl)piperidin-4-yl]cyclopropyl}ethyl)-5-(1H-tetrazol-1-yl)pyridin-2-amine

HRID 1039069Notes

Reaction equation

HRID 1039069 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.F[C:21]1[CH:26]=[CH:25][C:24]([N:27]2[CH:31]=[N:30][N:29]=[N:28]2)=[CH:23][N:22]=1.C(=O)([O-])[O-].[K+].[K+].O>CN1C(=O)CCC1>[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]=[CH:25][C:24]([N:27]4[CH:31]=[N:30][N:29]=[N:28]4)=[CH:23][N:22]=3)[CH2:10][CH2:9]2)=[N:6][CH:7]=1

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 677784742-{(1S,2S)-2-[1-(5-chloropyrimidin-2-yl)piperidin-4-yl]cyclopropyl}ethanamineHCID 67778750HCID 67778750, compound

Product 1

HCID 50939795N-(2-{(1S,2S)-2-[1-(5-chloropyrimidin-2-yl)piperidin-4-yl]cyclopropyl}ethyl)-5-(1H-tetrazol-1-yl)pyridin-2-amine

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
70 °C

Procedure

2-{(1S,2S)-2-[1-(5-chloropyrimidin-2-yl)piperidin-4-yl]cyclopropyl}ethanamine (50 mg, 0.18 mmol) from Example 5 step 3 and 2-fluoro-5-(1H-tetrazol-1-yl)pyridine (35.6 mg, 0.20 mmol) from step 1 were added in NMP (0.89 mL), then potassium carbonate (73.8 mg, 0.53 mmol) was added and the reaction was heated to 70° C. 6.5 hours. The reaction was cooled to room temperature, water (10 mL) was added, extracted with ethyl acetate (20 mL), second wash with brine (10 mL). The organic phase was 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 40% ethyl acetate/hexane to give the title compound as a white-solid.

Workup

  1. custom6.5 hours
  2. temperatureThe reaction was cooled to room temperature
  3. extractionextracted with ethyl acetate (20 mL)
  4. washsecond wash with brine (10 mL)
  5. dry with materialThe organic phase was dried 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 40% ethyl acetate/hexane

Sources & evidence

ORD record
ord-93941dec09fa4aab9936fc9c9ef0ff62
Source dataset
uspto-grants-2013_10
Patent number
US08552022B2

Reaction notes

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