1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride → (2S)-N2-3-[(cis)-2,6-dimethyl-1-piperidinyl]propyl-1-(5-methyl-1,3-benzoxazol-2-yl)-2-piperidinecarboxamide

HRID 1635631Notes

Reaction equation

HRID 1635631 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.[CH3:19][C@H:20]1[CH2:25][CH2:24][CH2:23][C@@H:22]([CH3:26])[N:21]1[CH2:27][CH2:28][CH2:29][NH2:30].Cl.[CH3:32]N(C)CCCN=C=NCC>ClCCl.CN(C)C1C=CN=CC=1>[CH3:19][C@H:20]1[CH2:25][CH2:24][CH2:23][C@@H:22]([CH3:26])[N:21]1[CH2:27][CH2:28][CH2:29][NH:30][C:16]([C@@H:11]1[CH2:12][CH2:13][CH2:14][CH2:15][N:10]1[C:2]1[O:1][C:5]2[CH:6]=[CH:7][C:8]([CH3:32])=[CH:9][C:4]=2[N:3]=1)=[O:18]

Participants

6

Reactant 3

HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 7176132cis-3-[2,6-Dimethylpiperidinyl]propylamineHCID 12050655(2S)-1-(1,3-benzoxazol-2-yl)-2-piperidinecarboxylic acid

Product 1

HCID 57249193(2S)-N2-3-[(cis)-2,6-dimethyl-1-piperidinyl]propyl-1-(5-methyl-1,3-benzoxazol-2-yl)-2-piperidinecarboxamideYield 8.5%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

(2S)-1-(1,3-Benzoxazol-2-yl)-2-piperidinecarboxylic acid (270 mg) [see Preparation 3] and 3-[(cis)-2,6-dimethyl-1-piperidinyl]propylamine (180 mg) [J. Am. Chem. Soc. (1971), 71, 3839 and references citied therein] were dissolved in dichloromethane (20 ml). 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (290 mg) and a catalytic amount of 4-dimethylaminopyridine were then added to the reaction mixture. The reaction mixture was then 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 sodium 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 20:1, by volume, dichloromethane:methanol to afford (2S)-N2-3-[(cis)-2,6-dimethyl-1-piperidinyl]propyl-1-(5-methyl-1,3-benzoxazol-2-yl)-2-piperidinecarboxamide (37 mg) as a 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 sodium sulphate
  5. customthe solvent removed under reduced pressure
  6. customThe crude product was purified by column chromatography on silica gel eluting with a solvent system of 20:1, by volume, dichloromethane

Sources & evidence

ORD record
ord-1c2db3936aeb4308a0cf906eb892cbb7
Source dataset
uspto-grants-2003_01
Patent number
US06509464B1

Reaction notes

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