Isopropyl iodide → 2-(2-(2-(2-((1-(1-Isopropylpiperidin-4-yl)-1H-pyrazol-4-yl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)propanamide

HRID 592470Notes

Reaction equation

HRID 592470 reaction equation
[NH:1]1[CH2:6][CH2:5][CH:4]([N:7]2[CH:11]=[C:10]([NH:12][C:13]3[N:18]=[C:17]([CH2:19][CH2:20][C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=4[CH:27]([CH3:31])[C:28]([NH2:30])=[O:29])[C:16]([C:32]([F:35])([F:34])[F:33])=[CH:15][N:14]=3)[CH:9]=[N:8]2)[CH2:3][CH2:2]1.I[CH:37]([CH3:39])[CH3:38].C([O-])([O-])=O.[K+].[K+]>CC#N>[CH:37]([N:1]1[CH2:2][CH2:3][CH:4]([N:7]2[CH:11]=[C:10]([NH:12][C:13]3[N:18]=[C:17]([CH2:19][CH2:20][C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=4[CH:27]([CH3:31])[C:28]([NH2:30])=[O:29])[C:16]([C:32]([F:34])([F:33])[F:35])=[CH:15][N:14]=3)[CH:9]=[N:8]2)[CH2:5][CH2:6]1)([CH3:39])[CH3:38]

Participants

5

Reactant 3

HCID 6362Isopropyl iodide2×HCID 11430Potassium CarbonateHCID 732951232-(2-(2-((1-(piperidin-4-yl)-1H-pyrazol-4-yl)amino)-5-(trifluoromethyl)pyrimidin-4-ylethyl)phenyl)propanamide

Product 1

HCID 732952952-(2-(2-(2-((1-(1-Isopropylpiperidin-4-yl)-1H-pyrazol-4-yl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)propanamideYield 70%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A suspension of 2-(2-(2-(2-((1-(piperidin-4-yl)-1H-pyrazol-4-yl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)propanamide A67 (80 mg, 0.16 mmol), 2-iodopropane (25 μL, 0.25 mmol) and K2CO3 (68 mg, 0.49 mmol) in MeCN (5 mL) was irradiated in the microwave at 120° C. for 40 minutes. Additional 2-iodopropane (25 μL, 0.25 mmol) was added and the reaction mixture was irradiated in the microwave at 120° C. for another 40 minutes. Upon cooling, the liquid was decanted from the solid and the volatiles were removed in vacuo. The resultant solid was suspended in water (50 mL) and sonicated for 10 minutes before being filtered. The solid was dissolved in acetone (3 mL) and precipitated by the addition of petroleum benzine 40-60° C. before being collected by filtration and dried under high vacuum to give the title compound 60 as a tan solid (61 mg, 70%). LCMS-D: rt 3.060 min; m/z 530.4 [M+H]+.

Workup

  1. customwas irradiated in the microwave at 120° C. for 40 minutes
  2. customthe reaction mixture was irradiated in the microwave at 120° C. for another 40 minutes
  3. temperatureUpon cooling
  4. customthe liquid was decanted from the solid
  5. customthe volatiles were removed in vacuo
  6. customsonicated for 10 minutes
  7. filtrationbefore being filtered
  8. dissolutionThe solid was dissolved in acetone (3 mL)
  9. customprecipitated by the addition of petroleum benzine 40-60° C.
  10. filtrationbefore being collected by filtration
  11. customdried under high vacuum

Sources & evidence

ORD record
ord-ac8edf49ff754472a6a85f052b556101
Source dataset
uspto-grants-2016_01
Patent number
US09238644B2

Reaction notes

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