Potassium Carbonate → 2-[(2-{(1S,2S)-2-[1-(5-chloropyrimidin-2-yl)piperidin-4-yl]cyclopropyl}ethyl)amino]-6-methylisonicotinonitrile

HRID 1039080Notes

Reaction equation

HRID 1039080 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.[K+].[K+].Cl[C:27]1[CH:28]=[C:29]([CH:32]=[C:33]([CH3:35])[N:34]=1)[C:30]#[N:31]>CS(C)=O.O>[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[CH:28]=[C:29]([CH:32]=[C:33]([CH3:35])[N:34]=3)[C:30]#[N:31])[CH2:10][CH2:9]2)=[N:6][CH:7]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 210854392-Chloro-6-methylpyridine-4-carbonitrileHCID 67778474HCID 67778474, compound

Product 1

HCID 509397902-[(2-{(1S,2S)-2-[1-(5-chloropyrimidin-2-yl)piperidin-4-yl]cyclopropyl}ethyl)amino]-6-methylisonicotinonitrile

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Conditions

Temperature
150 °C

Procedure

2-{(1S,2S)-2-[1-(5-chloropyrimidin-2-yl)piperidin-4-yl]cyclopropyl}ethanamine from step 3 of Example 5 (59 mg, 0.21 mmol) was dissolved in DMSO (1.0 ml). K2CO3 (86 mg, 0.62 mmol) and 2-chloro-6-methylisonicotinonitrile (31 mg, 0.21 mmol) from step 2 of this example were added and the mixture stirred at 150° C. overnight. The mixture was cooled to RT, diluted with water (30 ml), and extracted with EtOAc (3×30 ml). The organic fractions were combined, washed with brine, dried over Na2SO4, filtered and the volatiles removed in vacuum. The product was purified by chromatography on SiO2 eluting with 20% EtOAc:Hexanes to give the titled compound. LRMS calc: 396.18; obs: 397.27 (M+1).

Workup

  1. temperatureThe mixture was cooled to RT
  2. extractionextracted with EtOAc (3×30 ml)
  3. washwashed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. customthe volatiles removed in vacuum
  7. customThe product was purified by chromatography on SiO2 eluting with 20% EtOAc

Sources & evidence

ORD record
ord-1561ac73746c4e42b4ed827414ec8dc9
Source dataset
uspto-grants-2013_10
Patent number
US08552022B2

Reaction notes

Loading…