tert-Butyl 4-(4-((4-((3-carbamoyl-4-methylphenyl)ethynyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperazine-1-carboxylate → Tert-butyl 4-(4-((4-(3-carbamoyl-4-methylphenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperazine-1-carboxylate

HRID 1485205Notes

Reaction equation

HRID 1485205 reaction equation
[C:1]([C:4]1[CH:5]=[C:6]([C:11]#[C:12][C:13]2[C:18]([C:19]([F:22])([F:21])[F:20])=[CH:17][N:16]=[C:15]([NH:23][C:24]3[CH:29]=[CH:28][C:27]([N:30]4[CH2:35][CH2:34][N:33]([C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[CH2:32][CH2:31]4)=[CH:26][CH:25]=3)[N:14]=2)[CH:7]=[CH:8][C:9]=1[CH3:10])(=[O:3])[NH2:2]>CN(C=O)C.[Pd]>[C:1]([C:4]1[CH:5]=[C:6]([CH:7]=[CH:8][C:9]=1[CH3:10])[CH2:11][CH2:12][C:13]1[C:18]([C:19]([F:21])([F:22])[F:20])=[CH:17][N:16]=[C:15]([NH:23][C:24]2[CH:29]=[CH:28][C:27]([N:30]3[CH2:31][CH2:32][N:33]([C:36]([O:38][C:39]([CH3:40])([CH3:41])[CH3:42])=[O:37])[CH2:34][CH2:35]3)=[CH:26][CH:25]=2)[N:14]=1)(=[O:3])[NH2:2]

Participants

4

Reactant 1

HCID 71209810tert-Butyl 4-(4-((4-((3-carbamoyl-4-methylphenyl)ethynyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperazine-1-carboxylate

Product 1

HCID 68282839Tert-butyl 4-(4-((4-(3-carbamoyl-4-methylphenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperazine-1-carboxylateYield 32%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 6228DimethylformamideSolvent

Procedure

A mixture of tert-butyl 4-(4-((4-((3-carbamoyl-4-methylphenyl)ethynyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperazine-1-carboxylate (I72) (0.092 g, 0.16 mmol) and 10% Pd/C (0.116 g) in DMF (5 mL) was stirred over night under a H2 atmosphere. The mixture was filtered through Celite then concentrated under reduced pressure. The residue was then purified using silica gel column chromatography (0-100% EtOAc/petroleum benzine 40-60° C.) and the product triturated with methanol. The resulting precipitate was collected by vacuum filtration to give the title compound (I73) (29.5 mg, 32%); 1H NMR (400 MHz, d6-DMSO) δ 10.00 (s, 1H), 8.61 (s, 1H), 7.66 (s, 1H), 7.55 (d, J=9.0 Hz, 2H), 7.33 (s, 1H), 7.25 (s, 1H), 7.16 (m, 2H), 6.94 (d, J=9.1 Hz, 2H), 3.46 (m, 4H), 3.04 (m, 8H), 2.32 (s, 3H), 1.42 (s, 9H). LCMS Method C: rt 6.18 min; m/z 585.3 [M+H]+.

Workup

  1. filtrationThe mixture was filtered through Celite
  2. concentrationthen concentrated under reduced pressure
  3. customThe residue was then purified
  4. customsilica gel column chromatography (0-100% EtOAc/petroleum benzine 40-60° C.)
  5. customthe product triturated with methanol
  6. filtrationThe resulting precipitate was collected by vacuum filtration

Sources & evidence

ORD record
ord-bf714b0c6ffb4dfb9ddf9b1697298df7
Source dataset
uspto-grants-2016_08
Patent number
US09421205B2

Reaction notes

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