Pyridine → 1-Acetyl-piperidine-4-carboxylic acid {4-[(S)-3-((S)-2-methyl-pyrrolidin-1-yl)-cyclopentyl]-phenyl}-amide

HRID 1027436Notes

Reaction equation

HRID 1027436 reaction equation
[CH3:1][C@H:2]1[CH2:6][CH2:5][CH2:4][N:3]1[CH:7]1[CH2:11][CH2:10][C@H:9]([C:12]2[CH:17]=[CH:16][C:15]([NH2:18])=[CH:14][CH:13]=2)[CH2:8]1.[C:19]([N:22]1[CH2:27][CH2:26][CH:25]([C:28](Cl)=[O:29])[CH2:24][CH2:23]1)(=[O:21])[CH3:20].N1C=CC=CC=1.N.CO>ClCCCl.C(Cl)Cl>[CH3:1][C@H:2]1[CH2:6][CH2:5][CH2:4][N:3]1[CH:7]1[CH2:11][CH2:10][C@H:9]([C:12]2[CH:17]=[CH:16][C:15]([NH:18][C:28]([CH:25]3[CH2:24][CH2:23][N:22]([C:19](=[O:21])[CH3:20])[CH2:27][CH2:26]3)=[O:29])=[CH:14][CH:13]=2)[CH2:8]1

Participants

7

Reactant 4

HCID 1049PyridineHCID 1009501-Acetylpiperidine-4-carbonyl chlorideHCID 21705897Ammonia methanolHCID 674791474-[(S)-3-((S)-2-Methyl-pyrrolidin-1-yl)-cyclopentyl]-phenylamine2×

Product 1

HCID 682122911-Acetyl-piperidine-4-carboxylic acid {4-[(S)-3-((S)-2-methyl-pyrrolidin-1-yl)-cyclopentyl]-phenyl}-amideYield 63%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolvent2×HCID 6344DichloromethaneSolvent

Procedure

4-[(S)-3-((S)-2-Methyl-pyrrolidin-1-yl)-cyclopentyl]-phenylamine (Intermediate 14) was dissolved in DCE (1 mL). To this solution was transferred a solution of 1-acetyl-piperidine-4-carboxylic acid chloride in DCE (1 mL), followed by pyridine (0.5 mL). The solution was stirred at r.t. for 2 h when TLC (5% of 7N NH3 MeOH in DCM) and LC/MS showed that the reaction was complete. The reaction was quenched with polymer bound diethylenetriamine (4 mmol/g) (0.1 g) and the suspension was stirred for 30 min. Then, 10 mL of DCM was added to the suspension and the suspension was filtered through a celite pad, rinsed with DCM and 10% MeOH in DCM. The crude product was purified on a silica gel column eluted with 5% of 7N NH3 MeOH in DCM to obtain 15.9 mg (63%) of the title compound as a gummy solid.

Workup

  1. customThe reaction was quenched with polymer
  2. additionThen, 10 mL of DCM was added to the suspension
  3. filtrationthe suspension was filtered through a celite pad
  4. washrinsed with DCM and 10% MeOH in DCM
  5. customThe crude product was purified on a silica gel column
  6. washeluted with 5% of 7N NH3 MeOH in DCM

Sources & evidence

ORD record
ord-54aed7c316ef497fbc4d2176e6c9658f
Source dataset
uspto-grants-2014_05
Patent number
US08735385B2

Reaction notes

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