Potassium Carbonate → Ammonia

HRID 841921Notes

Reaction equation

HRID 841921 reaction equation
C(=O)([O-])[O-].[K+].[K+].[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][C@H:25]1[CH2:29][CH2:28][NH:27][CH2:26]1)=[O:23].Cl[CH2:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][N:33]=1.Cl.ClCC1C=CC=CN=1>C(#N)C>[NH3:9].[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][C@H:25]1[CH2:29][CH2:28][N:27]([CH2:31][C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][N:33]=2)[CH2:26]1)=[O:23]

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 23392Picolyl chloride hydrochlorideHCID 23393Picolyl chloride2×HCID 57068119(2S)-1-(1,3-benzoxazol-2-yl)-N2-[(3S)-pyrrolidin-3-yl]-2-piperidinecarboxamide

Product 2

HCID 222AmmoniaHCID 9887548(2S)-1-(1,3-benzoxazol-2-yl)-N2-[(3S)-1-(2-pyridinylmethyl)pyrrolidin-3-yl]-2-piperidinecarboxamide

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

Potassium carbonate (0.052 g) was added to a solution of (2S)-1-(1,3-benzoxazol-2-yl)-N2-[(3S)-pyrrolidin-3-yl]-2-piperidinecarboxamide (108.2 mg) [see Example 4] and 2-(chloromethyl)pyridine in acetonitrile (6.8 ml, 0.055M) at 0° C. [2-(Chloromethyl)pyridine was prepared from 2-(chloromethyl)pyridine hydrochloride by partitioning between diethyl ether and saturated. aqueous sodium hydrogen carbonate solution. The separated organic phase was washed with brine, dried over magnesium sulphate and the solvent removed under reduced pressure. The residual free base was immediately dissolved in acetonitrile and used]. The reaction mixture was stirred at room temperature for 18 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 system of 93:7:1, by volume, dichloromethane:methanol: 0.88 aqueous ammonia solution to afford (2S)-1-(1,3-benzoxazol-2-yl)-N2-[(3S)-1-(2-pyridinylmethyl)pyrrolidin-3-yl]-2-piperidinecarboxamide (63.1 mg) as an oil.

Workup

  1. customby partitioning between diethyl ether
  2. washThe separated organic phase was washed with brine
  3. dry with materialdried over magnesium sulphate
  4. customthe solvent removed under reduced pressure
  5. dissolutionThe residual free base was immediately dissolved in acetonitrile
  6. customafter which time the solvent was removed under reduced pressure
  7. customthe residue partitioned between ethyl acetate and water
  8. customThe organic layer was separated
  9. dry with materialdried over magnesium sulphate
  10. customthe solvent removed under reduced pressure
  11. customThe crude product was purified by column chromatography on silica gel eluting with a solvent system of 93:7:1, by volume, dichloromethane

Sources & evidence

ORD record
ord-1589b1cc040142e997b29d9db9fdf0b3
Source dataset
uspto-grants-2002_04
Patent number
US06372736B1

Reaction notes

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