Tert-butyl 4-(4-((4-((3-(2-methoxy-2-oxoethyl)pyridin-2-yl)ethynyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate → tert-Butyl 4-(4-((4-(2-(3-(2-methoxy-2-oxoethyl)pyridin-2-yl)ethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate

HRID 1485259Notes

Reaction equation

HRID 1485259 reaction equation
[CH3:1][O:2][C:3](=[O:43])[CH2:4][C:5]1[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]([CH: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)=[N:7][CH:8]=[CH:9][CH:10]=1>CN(C=O)C.[Pd]>[CH3:1][O:2][C:3](=[O:43])[CH2:4][C:5]1[C:6]([CH2:11][CH2:12][C:13]2[C:18]([C:19]([F:22])([F:20])[F:21])=[CH:17][N:16]=[C:15]([NH:23][C:24]3[CH:29]=[CH:28][C:27]([CH:30]4[CH2:35][CH2:34][N:33]([C:36]([O:38][C:39]([CH3:41])([CH3:40])[CH3:42])=[O:37])[CH2:32][CH2:31]4)=[CH:26][CH:25]=3)[N:14]=2)=[N:7][CH:8]=[CH:9][CH:10]=1

Participants

4

Reactant 1

HCID 71209391Tert-butyl 4-(4-((4-((3-(2-methoxy-2-oxoethyl)pyridin-2-yl)ethynyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate

Product 1

HCID 71208998tert-Butyl 4-(4-((4-(2-(3-(2-methoxy-2-oxoethyl)pyridin-2-yl)ethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylateYield 75%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 6228DimethylformamideSolvent2×

Procedure

A solution of tert-butyl 4-(4-((4-((3-(2-methoxy-2-oxoethyl)pyridin-2-yl)ethynyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate (I121) (81.5 mg, 0.137 mmol) in DMF (10 mL) was added to a solution of 10% Pd/C (170 mg) in DMF (7 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). The solvent was removed in vacuo to afford an oil which was purified on by column chromatography on silica gel (0-40% EtOAc in petroleum benzine 40-60° C.) to yield the title compound (I122) (61.4 mg, 75%) as a viscous oil; 1H NMR (400 MHz, CDCl3) δ 8.51 (s, 1H), 8.46 (dd, J=4.8, 1.7 Hz, 1H), 7.56-7.50 (m, 3H), 7.49 (s, 1H), 7.19-7.14 (m, 2H), 7.12 (dd, J=7.7, 4.8 Hz, 1H), 4.23 (bs, 2H), 3.72 (s, 2H), 3.70 (s, 3H), 3.40-3.33 (m, 2H), 3.32-3.23 (m, 2H), 2.80 (t, J=12.1 Hz, 2H), 2.62 (tt, J=12.1, 3.5 Hz, 1H), 1.81 (d, J=12.9 Hz, 2H), 1.65-1.55 (m, 2H), 1.48 (s, 9H). LCMS Method C: rt 6.01 min; m/z 622 [M+Na]+, 600 [M+H]+, 544 [M-tButyl+2H]+.

Workup

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

Sources & evidence

ORD record
ord-73f56da3a32f45d298fadcfc3abba696
Source dataset
uspto-grants-2016_08
Patent number
US09421205B2

Reaction notes

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