HCID 86712642, compound → HCID 86712643, compound

HRID 1778974Notes

Reaction equation

HRID 1778974 reaction equation
[CH3:1][O:2][C:3](=[O:40])[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]([CH3:19])=[CH:17][N:16]=[C:15]([NH:20][C:21]2[CH:22]=[CH:23][C:24]([CH:27]3[CH2:32][CH2:31][N:30]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[CH2:29][CH2:28]3)=[N:25][CH:26]=2)[N:14]=1>CN(C=O)C.CCN(CC)CC.[Pd]>[CH3:1][O:2][C:3](=[O:40])[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]([CH3:19])=[CH:17][N:16]=[C:15]([NH:20][C:21]2[CH:22]=[CH:23][C:24]([CH:27]3[CH2:28][CH2:29][N:30]([C:33]([O:35][C:36]([CH3:37])([CH3:38])[CH3:39])=[O:34])[CH2:31][CH2:32]3)=[N:25][CH:26]=2)[N:14]=1

Participants

5

Reactant 1

HCID 86712642HCID 86712642, compound

Product 1

HCID 86712643HCID 86712643, compound

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

A suspension of 10% Pd/C (53% water; 30 mg) and tert-butyl 4-(5-((4-((2-(2-methoxy-2-oxoethyl)phenyl)ethynyl)-5-methylpyrimidin-2-yl)amino)pyridin-2-yl)piperidine-1-carboxylate (A17) (125 mg, 0.231 mmol) in DMF (5 mL) and Et3N (1 mL) was stirred under a hydrogen atmosphere at room temperature for 44 hours. The resulting mixture was filtered through Celite, washing with EtOAc (200 mL). The combined filtrates were evaporated in vacuo and the resulting oil purified by silica gel chromatography (Biotage Isolera, 12 g SiO2 cartridge, 0-100% EtOAc in hexanes) to give the title compound A18 as a yellow foam (115 mg, 91%); 1H NMR (400 MHz, CDCl3) δ 8.62 (d, J=2.5 Hz, 1H), 8.16 (dd, J=8.5, 2.7 Hz, 1H), 8.11 (d, J=0.5 Hz, 1H), 7.25-7.16 (m, 5H), 7.11 (d, J=8.5 Hz, 1H), 4.25 (br. s, 2H), 3.71 (s, 2H), 3.67 (s, 3H), 3.09 (dd, J=9.6, 6.1 Hz, 2H), 2.93 (dd, J=9.4, 6.0 Hz, 2H), 2.88-2.76 (m, 3H), 2.08 (s, 3H), 1.91 (d, J=11.8 Hz, 2H), 1.75-1.61 (m, 2H), 1.47 (s, 9H). LCMS-A: rt 5.401 min; m/z 546 [M+H]+.

Workup

  1. filtrationThe resulting mixture was filtered through Celite
  2. washwashing with EtOAc (200 mL)
  3. customThe combined filtrates were evaporated in vacuo
  4. customthe resulting oil purified by silica gel chromatography (Biotage Isolera, 12 g SiO2 cartridge, 0-100% EtOAc in hexanes)

Sources & evidence

ORD record
ord-5c7bedf02e4a4c198fbb4afe5a569d23
Source dataset
uspto-grants-2016_02
Patent number
US09266864B2

Reaction notes

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