Cesium carbonate → trans 6-[(2-{2-[1-(5-Chloropyrimidin-2-yl)piperidin-4-yl]cyclopropyl}ethyl)amino]-2-methylpyrimidine-4-carbonitrile

HRID 1039107Notes

Reaction equation

HRID 1039107 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>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

5

Reactant 3

HCID 10796Cesium carbonateHCID 581284976-Chloro-2-methylpyrimidine-4-carbonitrileHCID 677774992-{(1S,2R)-2-[1-(5-chloropyrimidin-2-yl)piperidin-4-yl]cyclopropyl}ethanamine

Product 1

HCID 86666148trans 6-[(2-{2-[1-(5-Chloropyrimidin-2-yl)piperidin-4-yl]cyclopropyl}ethyl)amino]-2-methylpyrimidine-4-carbonitrile

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

2-{2-[1-(5-chloropyrimidin-2-yl)piperidin-4-yl]cyclopropyl}ethanamine from Example 60 Step 1 (50 mg, 0.178 mmol) was in 0.5 mL DMF. Cs2CO3 (290 mg, 0.890 mmol) was added. Reaction mixture was stirred at room temperature for 10 min before cooled to 0° C. in ice bath. 6-chloro-2-methylpyrimidine-4-carbonitrile from Example 5 step 4 (30.1 mg, 0.196 mmol) in 0.3 mL DMF was added via syringe. Reaction was stirred at 0° C. in ice bath for 2 hours. The mixture was quenched with ice water and aqueous phase was further extracted with ethyl acetate for 3 times. The combined organic layers were washed with water and brine, then dried over Na2SO4 and concentrated. The residue was purified by column chromatography eluting with 30% Ethyl acetate/hexane with 0.5% 2M NH3-MeOH to give the titled compound.

Workup

  1. customReaction mixture
  2. temperaturebefore cooled to 0° C. in ice bath
  3. customReaction
  4. stirringwas stirred at 0° C. in ice bath for 2 hours
  5. customThe mixture was quenched with ice water and aqueous phase
  6. extractionwas further extracted with ethyl acetate for 3 times
  7. washThe combined organic layers were washed with water and brine
  8. dry with materialdried over Na2SO4
  9. concentrationconcentrated
  10. customThe residue was purified by column chromatography
  11. washeluting with 30% Ethyl acetate/hexane with 0.5% 2M NH3-MeOH

Sources & evidence

ORD record
ord-6b2a1b58dfac4386964c308acafc69be
Source dataset
uspto-grants-2013_10
Patent number
US08552022B2

Reaction notes

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