tert-Butyl 4-(4-((4-((2-(1-methoxy-1-oxopropan-2-yl)phenyl)ethynyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate → Tert-butyl 4-(4-((4-(2-(1-methoxy-1-oxopropan-2-yl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate

HRID 1485184Notes

Reaction equation

HRID 1485184 reaction equation
[CH3:1][O:2][C:3](=[O:44])[CH:4]([C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=1[C:12]#[C:13][C:14]1[C:19]([C:20]([F:23])([F:22])[F:21])=[CH:18][N:17]=[C:16]([NH:24][C:25]2[CH:30]=[CH:29][C:28]([CH:31]3[CH2:36][CH2:35][N:34]([C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])[CH2:33][CH2:32]3)=[CH:27][CH:26]=2)[N:15]=1)[CH3:5]>CCOC(C)=O.CN(C=O)C.[Pd]>[CH3:1][O:2][C:3](=[O:44])[CH:4]([C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=1[CH2:12][CH2:13][C:14]1[C:19]([C:20]([F:22])([F:23])[F:21])=[CH:18][N:17]=[C:16]([NH:24][C:25]2[CH:30]=[CH:29][C:28]([CH:31]3[CH2:36][CH2:35][N:34]([C:37]([O:39][C:40]([CH3:41])([CH3:43])[CH3:42])=[O:38])[CH2:33][CH2:32]3)=[CH:27][CH:26]=2)[N:15]=1)[CH3:5]

Participants

5

Reactant 1

HCID 71209054tert-Butyl 4-(4-((4-((2-(1-methoxy-1-oxopropan-2-yl)phenyl)ethynyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate

Product 1

HCID 71209279Tert-butyl 4-(4-((4-(2-(1-methoxy-1-oxopropan-2-yl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylateYield 77.7%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalyst2×HCID 6228DimethylformamideSolvent3×HCID 8857Ethyl AcetateSolvent2×

Procedure

A solution of tert-butyl 4-(4-((4-((2-(1-methoxy-1-oxopropan-2-yl)phenyl)ethynyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate (I52) (0.108 g, 0.177 mmol) in EtOAc (5 mL) and DMF (10 mL) was added to a suspension of 10% Pd/C (80 mg) in EtOAc (5 mL). The reaction was stirred at room temperature for 24 hours under an atmosphere of hydrogen. The reaction was filtered and the solvent removed in vacuo to yield a brown residue. The residue was redissolved in DMF (15 mL) and added to a suspension of 10% Pd/C (55 mg) in DMF (5 mL). The reaction was stirred at room temperature for 24 hours under an atmosphere of hydrogen. The reaction was filtered through a pad of celite washing with EtOAc (100 mL). Removal of the solvent under reduced pressure yielded a brown viscous oil which was purified by column chromatography on silica gel (0-15% EtOAc in petroleum benzine 40-60° C.) to afford the title compound (I53) (84.3 mg, 77%) as a pale yellow viscous oil; 1H NMR (400 MHz, CDCl3) δ 8.54 (s, 1H), 7.59-7.54 (m, 2H), 7.38 (s, 1H), 7.33-7.30 (m, 1H), 7.25-7.17 (m, 5H), 4.25 (s, 2H), 4.11 (q, J=7.1 Hz, 1H), 3.64 (s, 3H), 3.23-3.02 (m, 4H), 2.81 (t, J=12.0 Hz, 2H), 2.64 (tt, J=12.0, 3.4 Hz, 1H), 1.83 (d, J=12.9 Hz, 2H), 1.67-1.59 (m, 2H), 1.50-1.48 (d, J=7.0 Hz, 3H; s, 9H). LCMS Method C: rt 7.15 min; m/z 635 [M+Na]+, 613 [M+H]+, 557 [M-tButyl+2H]+.

Workup

  1. filtrationThe reaction was filtered
  2. customthe solvent removed in vacuo
  3. customto yield a brown residue
  4. stirringThe reaction was stirred at room temperature for 24 hours under an atmosphere of hydrogen
  5. filtrationThe reaction was filtered through a pad of celite
  6. washwashing with EtOAc (100 mL)
  7. customRemoval of the solvent under reduced pressure
  8. customyielded a brown viscous oil which
  9. customwas purified by column chromatography on silica gel (0-15% EtOAc in petroleum benzine 40-60° C.)

Sources & evidence

ORD record
ord-850da4b3f8434f7bb4e24348598adf80
Source dataset
uspto-grants-2016_08
Patent number
US09421205B2

Reaction notes

Loading…