tert-Butyl 1-(4-(4-((2-(1-carbamoylcyclopropyl)phenyl)ethynyl)-5-(trifluoromethyl)pyrimidin-2-ylamino)phenyl)ethylcarbamate → tert-Butyl 1-(4-(4-(2-(1-carbamoylcyclopropyl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-ylamino)phenyl)ethylcarbamate

HRID 592493Notes

Reaction equation

HRID 592493 reaction equation
[C:1]([C:4]1([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=2[C:13]#[C:14][C:15]2[C:20]([C:21]([F:24])([F:23])[F:22])=[CH:19][N:18]=[C:17]([NH:25][C:26]3[CH:31]=[CH:30][C:29]([CH:32]([NH:34][C:35](=[O:41])[O:36][C:37]([CH3:40])([CH3:39])[CH3:38])[CH3:33])=[CH:28][CH:27]=3)[N:16]=2)[CH2:6][CH2:5]1)(=[O:3])[NH2:2]>CCOC(C)=O.CN(C=O)C.[Pd]>[C:1]([C:4]1([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=2[CH2:13][CH2:14][C:15]2[C:20]([C:21]([F:22])([F:24])[F:23])=[CH:19][N:18]=[C:17]([NH:25][C:26]3[CH:31]=[CH:30][C:29]([CH:32]([NH:34][C:35](=[O:41])[O:36][C:37]([CH3:40])([CH3:39])[CH3:38])[CH3:33])=[CH:28][CH:27]=3)[N:16]=2)[CH2:6][CH2:5]1)(=[O:3])[NH2:2]

Participants

5

Reactant 1

HCID 86712349tert-Butyl 1-(4-(4-((2-(1-carbamoylcyclopropyl)phenyl)ethynyl)-5-(trifluoromethyl)pyrimidin-2-ylamino)phenyl)ethylcarbamate

Product 1

HCID 73295800tert-Butyl 1-(4-(4-(2-(1-carbamoylcyclopropyl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-ylamino)phenyl)ethylcarbamateYield 56%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

A solution of tert-butyl 1-(4-(4-((2-(1-carbamoylcyclopropyl)phenyl)ethynyl)-5-(trifluoromethyl)pyrimidin-2-ylamino)phenyl)ethylcarbamate (0.25 g, 0.44 mmol) in EtOAc (12 mL) and DMF (2.0 mL) was stirred with Pd/C 10% (0.15 g) under an atmosphere of hydrogen for 16 hours at ambient temperature. The reaction mixture was diluted with EtOAc, filtered through a plug of Celite and washed with EtOAc. The solvents were removed in vacuo and the crude residue was purified by silica gel column chromatography (Combiflash Rf 0-100% EtOAc in cyclohexane) to give the title compound 70 as a colourless oil (0.14 g, 56%). LCMS-C: rt 5.88 min; m/z 570 [M+H]+.

Workup

  1. filtrationfiltered through a plug of Celite
  2. washwashed with EtOAc
  3. customThe solvents were removed in vacuo
  4. customthe crude residue was purified by silica gel column chromatography (Combiflash Rf 0-100% EtOAc in cyclohexane)

Sources & evidence

ORD record
ord-015c1c2d79b44cab817a4fe4b25bf2c2
Source dataset
uspto-grants-2016_01
Patent number
US09238644B2

Reaction notes

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