Potassium Carbonate → Ammonia

HRID 2119374Notes

Reaction equation

HRID 2119374 reaction equation
[CH:1]([N:4]=[C:5]=[O:6])([CH3:3])[CH3:2].[O:7]1[C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=2[N:9]=[C:8]1[N:16]1[CH2:21][CH2:20][CH2:19][CH2:18][C@H:17]1[C:22]([NH:24][CH2:25][CH2:26][N:27]1[C@H:32]([CH3:33])[CH2:31][NH:30][CH2:29][C@@H:28]1[CH3:34])=[O:23].C(=O)([O-])[O-].[K+].[K+]>C(#N)C>[NH3:4].[O:7]1[C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=2[N:9]=[C:8]1[N:16]1[CH2:21][CH2:20][CH2:19][CH2:18][C@H:17]1[C:22]([NH:24][CH2:25][CH2:26][N:27]1[C@@H:32]([CH3:33])[CH2:31][N:30]([C:5]([NH:4][CH:1]([CH3:3])[CH3:2])=[O:6])[CH2:29][C@H:28]1[CH3:34])=[O:23]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 61277Isopropyl isocyanateHCID 9821522(2S)-1-(1,3-benzoxazol-2-yl)-N2-2-[(cis)-2,6-dimethyl-1-piperazinyl]ethyl-2-piperidinecarboxamide

Product 2

HCID 222AmmoniaHCID 9869349(cis)-4-[2-([(2S)-1-(1,3-benzoxazol-2-yl)-2-piperidinyl]carbonylamino)ethyl]-N1-isopropyl-3,5-dimethyl-1-piperazinecarboxamide

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

Isopropylisocyanate (0.029 ml) was added to a solution of (2S)-1-(1,3-benzoxazol-2-yl)-N2-2-[(cis)-2,6-dimethyl-1-piperazinyl]ethyl-2-piperidinecarboxamide (105 mg) [see Example 8] and potassium carbonate (37.5 mg) in acetonitrile (3 ml). The reaction mixture was stirred at room temperature for 5 hours, after which time the solvent was removed under reduced pressure and the residue partitioned between ethyl acetate and water. The organic layer was separated, dried over magnesium sulphate and the solvent removed under reduced pressure. The crude product was purified by column chromatography on silica gel eluting with a solvent gradient of 94.6:5.6:0.8 changing to 93:7; 1, by volume, dichloromethane:methanol:0.88 aqueous ammonia solution to afford (cis)-4-[2-([(2S)-1-(1,3-benzoxazol-2-yl)-2-piperidinyl]carbonylamino)ethyl]-N1-isopropyl-3,5-dimethyl-1-piperazinecarboxamide (72.8 mg) as a white solid.

Workup

  1. customafter which time the solvent was removed under reduced pressure
  2. customthe residue partitioned between ethyl acetate and water
  3. customThe organic layer was separated
  4. dry with materialdried over magnesium sulphate
  5. customthe solvent removed under reduced pressure
  6. customThe crude product was purified by column chromatography on silica gel eluting with a solvent gradient of 94.6:5.6:0.8 changing to 93:7

Sources & evidence

ORD record
ord-c989c02e86c34b139e6a163f2323f3f0
Source dataset
uspto-grants-2004_02
Patent number
US06686357B1

Reaction notes

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