Methanol → 1-(2-(2-(2-((6-Methoxypyridin-3-yl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)cyclopropanecarboxamide

HRID 592480Notes

Reaction equation

HRID 592480 reaction equation
[CH3:1][O:2][C:3]1[N:8]=[CH:7][C:6]([NH:9][C:10]2[N:15]=[C:14]([C:16]#[C:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=3[C:24]3([C:27]([NH2:29])=[O:28])[CH2:26][CH2:25]3)[C:13]([C:30]([F:33])([F:32])[F:31])=[CH:12][N:11]=2)=[CH:5][CH:4]=1.CO>CCOC(C)=O.[Pd]>[CH3:1][O:2][C:3]1[N:8]=[CH:7][C:6]([NH:9][C:10]2[N:15]=[C:14]([CH2:16][CH2:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=3[C:24]3([C:27]([NH2:29])=[O:28])[CH2:26][CH2:25]3)[C:13]([C:30]([F:32])([F:33])[F:31])=[CH:12][N:11]=2)=[CH:5][CH:4]=1

Participants

5

Reactant 2

HCID 887MethanolHCID 867123441-(2-((2-((6-Methoxypyridin-3-yl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethynyl)phenyl)cyclopropanecarboxamide

Product 1

HCID 732954661-(2-(2-(2-((6-Methoxypyridin-3-yl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)cyclopropanecarboxamideYield 56%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalyst2×HCID 8857Ethyl AcetateSolvent2×

Procedure

A solution of 1-(2-((2-((6-methoxypyridin-3-yl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethynyl)phenyl)cyclopropanecarboxamide A73 (0.229 g, 0.505 mmol) in EtOAc (20 mL) was stirred over 10% Pd/C (wetted with ca. 53% water, 0.150 g) under an atmosphere of hydrogen for 16 hours. The mixture was filtered through Celite and the solvent was removed in vacuo. Purification by column chromatography (Biotage Isolera, 40 g SiO2, 0-80% EtOAc in petroleum benzine 40-60° C.) gave an off-white solid contaminated with alkyne starting material. The solid was dissolved in EtOAc (20 mL) and MeOH (10 mL) and stirred over 10% Pd/C (wetted with ca. 53% water, 0.130 g) for 16 hours under an atmosphere of hydrogen. The mixture was filtered through Celite and the solvent was removed in vacuo to give the title compound 64 as a white solid (0.130 g, 56%). LCMS-D: rt 3.51 min; m/z 458 [M+H]+.

Workup

  1. filtrationThe mixture was filtered through Celite
  2. customthe solvent was removed in vacuo
  3. customPurification by column chromatography (Biotage Isolera, 40 g SiO2, 0-80% EtOAc in petroleum benzine 40-60° C.)
  4. customgave an off-white solid
  5. filtrationThe mixture was filtered through Celite
  6. customthe solvent was removed in vacuo

Sources & evidence

ORD record
ord-dd50221f7c6048368e3fb4bca13f30a8
Source dataset
uspto-grants-2016_01
Patent number
US09238644B2

Reaction notes

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