Tris(hydroxymethyl)aminomethane → 1,1-dimethylethyl (2R,6S)-4-{[4-(2-{4-[(4-fluorophenyl)amino]-1-piperidinyl}-1,1-dimethyl-2-oxoethyl)phenyl]methyl}-2,6-dimethyl-1-piperazinecarboxylate

HRID 43362Notes

Reaction equation

HRID 43362 reaction equation
[CH3:1][C:2]([O:5][C:6]([N:8]1[C@@H:13]([CH3:14])[CH2:12][N:11]([CH2:15][C:16]2[CH:21]=[CH:20][C:19]([C:22]([CH3:27])([CH3:26])[C:23]([OH:25])=O)=[CH:18][CH:17]=2)[CH2:10][C@H:9]1[CH3:28])=[O:7])([CH3:4])[CH3:3].C1CCC(N=C=NC2CCCCC2)CC1.ON1C2C=CC=CC=2N=N1.[F:54][C:55]1[CH:60]=[CH:59][C:58]([NH:61][CH:62]2[CH2:67][CH2:66][NH:65][CH2:64][CH2:63]2)=[CH:57][CH:56]=1.C(O)C(N)(CO)CO.[N-]=C=O>CN(C=O)C.C(Cl)Cl>[F:54][C:55]1[CH:60]=[CH:59][C:58]([NH:61][CH:62]2[CH2:67][CH2:66][N:65]([C:23](=[O:25])[C:22]([C:19]3[CH:18]=[CH:17][C:16]([CH2:15][N:11]4[CH2:12][C@H:13]([CH3:14])[N:8]([C:6]([O:5][C:2]([CH3:3])([CH3:1])[CH3:4])=[O:7])[C@H:9]([CH3:28])[CH2:10]4)=[CH:21][CH:20]=3)([CH3:26])[CH3:27])[CH2:64][CH2:63]2)=[CH:57][CH:56]=1

Participants

8

Reactant 6

HCID 6503Tris(hydroxymethyl)aminomethaneHCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 105034IsocyanateHCID 4778193N-(4-Fluorophenyl)-4-piperidinamineHCID 252242082-{4-[((3R,5S)-4-{[(1,1-Dimethylethyl)oxy]carbonyl}-3,5-dimethyl-1-piperazinyl)methyl]phenyl}-2-methylpropanoic Acid

Product 1

HCID 252227911,1-dimethylethyl (2R,6S)-4-{[4-(2-{4-[(4-fluorophenyl)amino]-1-piperidinyl}-1,1-dimethyl-2-oxoethyl)phenyl]methyl}-2,6-dimethyl-1-piperazinecarboxylate

Reagents, catalysts & solvents 1

HCID 22350042dichloromethane N,N-dimethylformamideSolvent

Procedure

A mixture of D48 (100 mg, 0.256 mmol), polymer-supported DCC (296 mg, 1.3 mmol/g, 0.385 mmol) and 1-hydroxybenzotriazole (18 mg, 0.128 mmol) in 1:4 DMF/DCM (5 ml) was treated with D2 (50 mg, 0.256 mmol) and the mixture stirred overnight. Scavenger resins (PS-trisamine, PS-isocyanate and Si-carbonate) were added, the mixture was shaken for 2 h and then filtered and concentrated to give 1,1-dimethylethyl (2R,6S)-4-{[4-(2-{4-[(4-fluorophenyl)amino]-1-piperidinyl}-1,1-dimethyl-2-oxoethyl)phenyl]methyl}-2,6-dimethyl-1-piperazinecarboxylate, MS (ES): MH+ 567. This whole was treated with 4M HCl in 1,4-dioxane (2 ml) for 1 h. The solvents were removed in vacuo to give the dihydrochloride salt of the title compound (115 mg). MS (ES): MH+ 467.

Workup

  1. stirringthe mixture was shaken for 2 h
  2. filtrationfiltered
  3. concentrationconcentrated

Sources & evidence

ORD record
ord-81684a08a5244ad0b209e78d006c81ff
Source dataset
uspto-grants-2013_09
Patent number
US08536182B2

Reaction notes

Loading…