tert-Butyl (3R)-3-(aminomethyl)piperidine-1-carboxylate → N-(2-{3-({(3R)-1-(tert-butoxycarbonyl)-3-piperidyl}methyl)amino-3-oxopropyl}amino-2-oxoethyl)-3,3,3-triphenylpropanamide

HRID 272064Notes

Reaction equation

HRID 272064 reaction equation
[NH2:1][CH2:2][C@H:3]1[CH2:8][CH2:7][CH2:6][N:5]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:4]1.[C:16]1([C:22]([C:42]2[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=2)([C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)[CH2:23][C:24]([NH:26][CH2:27][C:28]([NH:30][CH2:31][CH2:32][C:33](O)=[O:34])=[O:29])=[O:25])[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.O.ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C>CN(C)C=O.C(Cl)(Cl)Cl.C(N(CC)CC)C>[C:12]([O:11][C:9]([N:5]1[CH2:6][CH2:7][CH2:8][C@H:3]([CH2:2][NH:1][C:33](=[O:34])[CH2:32][CH2:31][NH:30][C:28](=[O:29])[CH2:27][NH:26][C:24](=[O:25])[CH2:23][C:22]([C:36]2[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=2)([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[C:42]2[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=2)[CH2:4]1)=[O:10])([CH3:15])([CH3:14])[CH3:13]

Participants

8

Reactant 4

HCID 1502023tert-Butyl (3R)-3-(aminomethyl)piperidine-1-carboxylateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 110045083-(2-{(3,3,3-Triphenylpropanoyl)amino}acetylamino)propionic acid

Product 1

HCID 11734836N-(2-{3-({(3R)-1-(tert-butoxycarbonyl)-3-piperidyl}methyl)amino-3-oxopropyl}amino-2-oxoethyl)-3,3,3-triphenylpropanamideYield 88%

Reagents, catalysts & solvents 3

HCID 6212ChloroformSolventHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

To a solution of 0.55 g of (3R)-3-aminomethyl-1-(tert-butoxycarbonyl)piperidine and 1.1 g of 3-(2-{(3,3,3-triphenylpropanoyl)amino}acetylamino)propionic acid in 10 ml of N,N-dimethylformamide, 0.52 g of 1-hydroxybenzotriazole monohydrate and 0.75 g of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide monohydrochloride were successively added at room temperature, and stirred for 2 hours at the same temperature. Then 2.0 ml of triethylamine and 10 ml of chloroform were added at room temperature, followed by an hour's stirring. The reaction liquid was distilled off under reduced pressure, diluted with ethyl acetate, washed successively with saturated aqueous sodium bicarbonate solution, 10% aqueous citric acid solution and saturated saline solution, and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure and the residue was purified by means of silica gel column chromatography (eluting solvent: chloroform/methanol=19/1) to provide 1.41 g of the title compound.

Workup

  1. waitfollowed by an hour
  2. stirring's stirring
  3. customThe reaction liquid
  4. distillationwas distilled off under reduced pressure
  5. additiondiluted with ethyl acetate
  6. washwashed successively with saturated aqueous sodium bicarbonate solution, 10% aqueous citric acid solution and saturated saline solution
  7. dry with materialdried over anhydrous magnesium sulfate
  8. distillationThe solvent was distilled off under reduced pressure
  9. customthe residue was purified by means of silica gel column chromatography (eluting solvent: chloroform/methanol=19/1)

Sources & evidence

ORD record
ord-36e2dc2c5d40418da4009f07ec7cabaa
Source dataset
uspto-grants-2008_11
Patent number
US07452908B2

Reaction notes

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