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

HRID 1485178Notes

Reaction equation

HRID 1485178 reaction equation
[CH3:1][O:2][C:3](=[O:43])[CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[C:11]#[C:12][C:13]1[C:18]([C:19]([F:22])([F:21])[F:20])=[CH:17][N:16]=[C:15]([NH:23][C:24]2[CH:29]=[CH:28][C:27]([CH:30]3[CH2:35][CH2:34][N:33]([C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[CH2:32][CH2:31]3)=[CH:26][CH:25]=2)[N:14]=1>CN(C=O)C.[Pd]>[CH3:1][O:2][C:3](=[O:43])[CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[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]([CH:30]3[CH2:31][CH2:32][N:33]([C:36]([O:38][C:39]([CH3:41])([CH3:42])[CH3:40])=[O:37])[CH2:34][CH2:35]3)=[CH:26][CH:25]=2)[N:14]=1

Participants

4

Reactant 1

HCID 71209070tert-Butyl 4-(4-((4-((2-(2-methoxy-2-oxoethyl)phenyl)ethynyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate

Product 1

HCID 68283243tert-Butyl 4-(4-((4-(2-(2-methoxy-2-oxoethyl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 6228DimethylformamideSolvent2×

Procedure

A solution of tert-butyl 4-(4-((4-((2-(2-methoxy-2-oxoethyl)phenyl)ethynyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate (I46) (0.157 g, 0.264 mmol) in DMF (15 mL) was added to a solution of 10% Pd/C (95 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 and washed through with EtOAc (100 mL). The solvent was removed in vacuo to afford a pale yellow oil which was purified by column chromatography on silica gel (0-20% EtOAc in petroleum benzine 40-60° C.) to yield the title compound (I47) (0.128 g, 81%) as a pale yellow viscous oil; 1H NMR (400 MHz, CDCl3) δ 8.53 (d, J=0.4 Hz, 1H), 7.59-7.54 (m, 2H), 7.39 (s, 1H), 7.28-7.17 (m, peaks obscured by CDCl3), 4.25 (bs, 2H), 3.75 (s, 2H), 3.68 (s, 3H), 3.17-3.04 (m, 4H), 2.81 (t, J=12.1 Hz, 2H), 2.64 (tt, J=11.8, 3.4 Hz, 1H), 1.83 (d, J=13.0 Hz, 2H), 1.67-1.59 (m, 2H), 1.49 (s, 9H). LCMS Method C: rt 7.02 min; m/z 621 [M+Na]+, 599 [M+H]+, 543 [M-tButyl+2H]+, 499 [M-Boc+2H]+.

Workup

  1. filtrationThe reaction was filtered through a pad of celite
  2. washwashed through with EtOAc (100 mL)
  3. customThe solvent was removed in vacuo
  4. customto afford a pale yellow oil which
  5. customwas purified by column chromatography on silica gel (0-20% EtOAc in petroleum benzine 40-60° C.)

Sources & evidence

ORD record
ord-b8ba9b5f46094a21bec03dfe42bf934f
Source dataset
uspto-grants-2016_08
Patent number
US09421205B2

Reaction notes

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