(3R)-1-benzylpyrrolidin-3-amine → (2S)-1-(1,3-benzoxazol-2-yl)-N2-[(3R)-1-benzylpyrrolidin-3-yl]-2-piperidinecarboxamide

HRID 412634Notes

Reaction equation

HRID 412634 reaction equation
[O:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[N:10]1[CH2:15][CH2:14][CH2:13][CH2:12][C@H:11]1[C:16]([OH:18])=O.O.ON1C2C=CC=CC=2N=N1.[CH2:30]([N:37]1[CH2:41][CH2:40][C@@H:39]([NH2:42])[CH2:38]1)[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1.Cl.CN(C)CCCN=C=NCC>ClCCl.O.C(N(CC)CC)C>[NH3:3].[O:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[N:10]1[CH2:15][CH2:14][CH2:13][CH2:12][C@H:11]1[C:16]([NH:42][C@@H:39]1[CH2:40][CH2:41][N:37]([CH2:30][C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[CH2:38]1)=[O:18]

Participants

9

Reactant 4

HCID 1519354(3R)-1-benzylpyrrolidin-3-amineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 12050655(2S)-1-(1,3-benzoxazol-2-yl)-2-piperidinecarboxylic acid

Product 2

HCID 222AmmoniaHCID 57172017(2S)-1-(1,3-benzoxazol-2-yl)-N2-[(3R)-1-benzylpyrrolidin-3-yl]-2-piperidinecarboxamideYield 114.5%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8471TriethylamineSolvent

Procedure

Triethylamine (0.167 ml) was added to a solution of (2S)-1-(1,3-benzoxazol-2-yl)-2-piperidinecarboxylic acid (100 mg) [see Preparation 3], 1-hydroxybenzotriazole hydrate (60.4 mg), (3R)-1-benzylpyrrolidin-3-ylamine (78.7 mg) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (85.4 mg) in dichloromethane (30 ml). The reaction mixture was stirred at room temperature for 18 hours, after which time the mixture was diluted with water and the organic layer was separated, dried over anhydrous sodium 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 50:50:0, changing to 25:75:0, changing to 20:80:1, by volume, hexane:ethyl acetate:0.88 aqueous ammonia solution to afford (2S)-1-(1,3-benzoxazol-2-yl)-N2-[(3R)-1-benzylpyrrolidin-3-yl]-2-piperidinecarboxamide as a yellow oil (94 mg).

Workup

  1. customthe organic layer was separated
  2. dry with materialdried over anhydrous sodium sulphate
  3. customthe solvent removed under reduced pressure
  4. customThe crude product was purified by column chromatography on silica gel eluting with a solvent gradient of 50:50:0

Sources & evidence

ORD record
ord-8bcbe07445844733954a53a18784b162
Source dataset
uspto-grants-2003_05
Patent number
US06562964B1

Reaction notes

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