Hydrochloric Acid → 2-[1-[(2,5-dimethylphenyl)acetyl]-4-piperidinyl]-N-methyl-N-[(1R)-1-phenylpropyl]-4-thiazolecarboxamide

HRID 2043714Notes

Reaction equation

HRID 2043714 reaction equation
[CH3:1][N:2]([C@@H:16]([C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[CH2:17][CH3:18])[C:3]([C:5]1[N:6]=[C:7]([CH:10]2[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]2)[S:8][CH:9]=1)=[O:4].C(N(CC)CC)C.[CH3:32][C:33]1[CH:38]=[CH:37][C:36]([CH3:39])=[CH:35][C:34]=1[CH2:40][C:41](O)=[O:42].Cl.CN(C)CCCN=C=NCC.Cl>ClCCl.CN(C)C1C=CN=CC=1>[CH3:32][C:33]1[CH:38]=[CH:37][C:36]([CH3:39])=[CH:35][C:34]=1[CH2:40][C:41]([N:13]1[CH2:14][CH2:15][CH:10]([C:7]2[S:8][CH:9]=[C:5]([C:3]([N:2]([CH3:1])[C@@H:16]([C:19]3[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=3)[CH2:17][CH3:18])=[O:4])[N:6]=2)[CH2:11][CH2:12]1)=[O:42]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 836152,5-Dimethylphenylacetic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 67461678N-methyl-N-[(1R)-1-phenylpropyl]-2-(4-piperidinyl)-4-thiazolecarboxamide2×

Product 1

HCID 674615172-[1-[(2,5-dimethylphenyl)acetyl]-4-piperidinyl]-N-methyl-N-[(1R)-1-phenylpropyl]-4-thiazolecarboxamide

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

N-Methyl-N-[(1R)-1-phenylpropyl]-2-(4-piperidinyl)-4-thiazolecarboxamide (i.e. the product of Example 1, Step E) (206 mg, 0.6 mmol) was dissolved in 4 mL of dry dichloromethane. To this reaction mixture was added triethylamine (90 μL, 0.65 mmol), 2,5-dimethylbenzeneacetic acid (98 mg, 0.6 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (125 mg, 0.65 mmol) and a catalytic amount of 4-(dimethylamino)pyridine (˜1 mg). The mixture was shaken overnight at ambient temperature, passed through a 5 mL capacity ChemEluten™, diatomaceous filter tube, pretreated with 3 mL of 1 N aqueous hydrochloric acid solution and eluted with 2 column volumes of dichloromethane. The dichloromethane solution was concentrated under reduced pressure, and the residue was purified by silica gel chromatography using acetone to give 276 mg of the title product, a compound of the present invention as a light yellow oil.

Workup

  1. washeluted with 2 column volumes of dichloromethane
  2. concentrationThe dichloromethane solution was concentrated under reduced pressure
  3. customthe residue was purified by silica gel chromatography

Sources & evidence

ORD record
ord-08d547ce56bb4273b605820767fecc0e
Source dataset
uspto-grants-2013_11
Patent number
US08586611B2

Reaction notes

Loading…