Triethylamine → tert-Butyl 4-(4-((4-(3-carbamoylphenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)benzyl)piperazine-1-carboxylate

HRID 1485282Notes

Reaction equation

HRID 1485282 reaction equation
[C:1]([C:4]1[CH:5]=[C:6]([C:10]#[C:11][C:12]2[C:17]([C:18]([F:21])([F:20])[F:19])=[CH:16][N:15]=[C:14]([NH:22][C:23]3[CH:42]=[CH:41][C:26]([CH2:27][N:28]4[CH2:33][CH2:32][N:31]([C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[CH2:30][CH2:29]4)=[CH:25][CH:24]=3)[N:13]=2)[CH:7]=[CH:8][CH:9]=1)(=[O:3])[NH2:2].C(N(CC)CC)C>CN(C=O)C.[Pd]>[C:1]([C:4]1[CH:5]=[C:6]([CH:7]=[CH:8][CH:9]=1)[CH2:10][CH2:11][C:12]1[C:17]([C:18]([F:21])([F:19])[F:20])=[CH:16][N:15]=[C:14]([NH:22][C:23]2[CH:24]=[CH:25][C:26]([CH2:27][N:28]3[CH2:29][CH2:30][N:31]([C:34]([O:36][C:37]([CH3:38])([CH3:39])[CH3:40])=[O:35])[CH2:32][CH2:33]3)=[CH:41][CH:42]=2)[N:13]=1)(=[O:3])[NH2:2]

Participants

5

Reactant 2

HCID 8471TriethylamineHCID 71208949Tert-butyl 4-(4-((4-((3-carbamoylphenyl)ethynyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)benzyl)piperazine-1-carboxylate

Product 1

HCID 71229334tert-Butyl 4-(4-((4-(3-carbamoylphenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)benzyl)piperazine-1-carboxylateYield 63%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 6228DimethylformamideSolvent

Procedure

A suspension of tert-butyl 4-(4-((4-((3-carbamoylphenyl)ethynyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)benzyl)piperazine-1-carboxylate (I145) (105 mg, 0.18 mmol) and Pd/C (75 mg) was stirred in DMF (5 mL) and triethylamine (0.15 mL) at 30° C. under hydrogen for 18 hours. After filtration the volatiles were evaporated under reduced pressure and the residue chromatographed (Biotage Isolera: 4 g silica cartridge, 0-2% methanol/ethyl acetate) to give the title compound (I146) (66.6 mg, 63% yield) as a white solid; 1H NMR (400 MHz, d6-DMSO) δ 10.20 (s, 1H), 8.67 (s, 1H), 7.93 (s, 1H), 7.79 (s, 1H), 7.74-7.50 (m, 8H), 7.40-7.35 (m, 2H), 7.33 (s, 1H), 7.24 (d, J=8.6 Hz, 2H), 3.43 (s, 2H), 3.17-3.04 (m, 4H), 2.36-2.23 (m, 4H), 1.38 (s, 9H). LCMS Method C: rt 5.05 min; m/z 585.2 [M+H]+; m/z 583.2 [M−H]−.

Workup

  1. filtrationAfter filtration the volatiles
  2. customwere evaporated under reduced pressure
  3. customthe residue chromatographed (Biotage Isolera: 4 g silica cartridge, 0-2% methanol/ethyl acetate)

Sources & evidence

ORD record
ord-62da7b0819654f49840edc5d613ec495
Source dataset
uspto-grants-2016_08
Patent number
US09421205B2

Reaction notes

Loading…