1-Propanol → N-cyclopropyl-4-[8-(isobutylamino)-6-(4-vinylphenyl)imidazo[1,2-a]pyrazin-3-yl]benzamide

HRID 925595Notes

Reaction equation

HRID 925595 reaction equation
Br[C:2]1[N:3]=[C:4]([NH:23][CH2:24][CH:25]([CH3:27])[CH3:26])[C:5]2[N:6]([C:8]([C:11]3[CH:22]=[CH:21][C:14]([C:15]([NH:17][CH:18]4[CH2:20][CH2:19]4)=[O:16])=[CH:13][CH:12]=3)=[CH:9][N:10]=2)[CH:7]=1.[CH:28]([C:30]1[CH:35]=[CH:34][C:33](B(O)O)=[CH:32][CH:31]=1)=[CH2:29].C(O)CC.C(=O)([O-])[O-].[K+].[K+]>C1(C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)[Pd][P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O>[CH:18]1([NH:17][C:15](=[O:16])[C:14]2[CH:21]=[CH:22][C:11]([C:8]3[N:6]4[CH:7]=[C:2]([C:33]5[CH:34]=[CH:35][C:30]([CH:28]=[CH2:29])=[CH:31][CH:32]=5)[N:3]=[C:4]([NH:23][CH2:24][CH:25]([CH3:27])[CH3:26])[C:5]4=[N:10][CH:9]=3)=[CH:12][CH:13]=2)[CH2:20][CH2:19]1

Participants

8

Reactant 4

HCID 10311-PropanolHCID 11430Potassium CarbonateHCID 27343934-Vinylphenylboronic acidHCID 509145924-(6-Bromo-8-(isobutylamino)imidazo[1,2-a]pyrazin-3-yl)-N-cyclopropylbenzamide

Product 1

HCID 57407262N-cyclopropyl-4-[8-(isobutylamino)-6-(4-vinylphenyl)imidazo[1,2-a]pyrazin-3-yl]benzamideYield 97%

Reagents, catalysts & solvents 3

HCID 11776TriphenylphosphineCatalystHCID 178419050HCID 178419050, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 0.5 g (1.17 mmol) 4-{6-bromo-8-[(2-methylpropyl)amino]imidazo[1,2-a]pyrazin-3-yl}-N-cyclopropylbenzamide (intermediate example 6-1), 345 mg (4-ethenylphenyl)boronic acid, 17 mL n-propanol, 1.75 mL of an aqueous 2M potassium carbonate solution, 15 mg triphenylphosphine, and 82 mg bis(triphenylphosphine)palladium was stirred at 120° C. for 2 hours. The solution was cooled, water added and extracted with dichloromethane. The organic phase was dried over sodium sulfate. After filtration and removal of solvent the residue was subjected to a column chromatography on silica gel to give 509 mg (97%) of the title compound. 1H-NMR (CDCl3): δ=0.67 (2H), 0.92 (2H), 1.06 (3H), 1.08 (3H), 2.09 (1H), 2.95 (1H), 3.58 (2H), 5.28 (1H), 5.80 (1H), 6.13 (1H), 6.34 (1H), 6.75 (1H), 7.47 (2H), 7.59 (1H), 7.65 (2H), 7.87 (2H), 7.92 (2H), 7.95 (1H) ppm.

Workup

  1. temperatureThe solution was cooled
  2. extractionextracted with dichloromethane
  3. dry with materialThe organic phase was dried over sodium sulfate
  4. filtrationAfter filtration and removal of solvent the residue

Sources & evidence

ORD record
ord-8f9d0eb895514e74a655e8ead0598313
Source dataset
uspto-grants-2016_03
Patent number
US09284317B2

Reaction notes

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