Tetrabutylammonium Fluoride → N-cyclopropyl-4-{6-[5-(methylamino)-5-oxopent-1-yn-1-yl]-8-[(2-methylpropyl)amino]imidazo[1,2-a]pyrazin-3-yl}benzamide

HRID 925600Notes

Reaction equation

HRID 925600 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.[CH3:28][NH:29][C:30](=[O:35])[CH2:31][CH2:32][C:33]#[CH:34].[F-].C([N+](CCCC)(CCCC)CCCC)CCC>C1COCC1.Cl[Pd]Cl.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[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:34]#[C:33][CH2:32][CH2:31][C:30]([NH:29][CH3:28])=[O:35])[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

6

Reactant 3

HCID 2724141Tetrabutylammonium FluorideHCID 15210994N-methylpent-4-ynamideHCID 509145924-(6-Bromo-8-(isobutylamino)imidazo[1,2-a]pyrazin-3-yl)-N-cyclopropylbenzamide

Product 1

HCID 54765762N-cyclopropyl-4-{6-[5-(methylamino)-5-oxopent-1-yn-1-yl]-8-[(2-methylpropyl)amino]imidazo[1,2-a]pyrazin-3-yl}benzamideYield 44%

Reagents, catalysts & solvents 2

HCID 13169693Triphenylphosphine palladium dichlorideCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 128 mg (0.3 mmol) 4-{6-bromo-8-[(2-methylpropyl)amino]imidazo[1,2-a]pyrazin-3-yl}-N-cyclopropylbenzamide in 1 mL THF were added 133 mg (1.2 mmol) N-methylpent-4-ynamide, 42 mg (0.06 mmol dichloropalladium-triphenylphosphane (1:2) and 363 mg (1.5 mmol) tetrabutylammoniumfluoride and the mixture was heated at 80° C. for 180 min in a microwave tube. The mixture was evaporated, redissolved in 2 mL DMSO, filtered and purified by HPLC to yield 60 mg (44%) of the title compound. UPLC-MS: RT=1.01 min; m/z (ES+) 459.6 [MH+]; required MW=458.6.

Workup

  1. customThe mixture was evaporated
  2. dissolutionredissolved in 2 mL DMSO
  3. filtrationfiltered
  4. custompurified by HPLC

Sources & evidence

ORD record
ord-5706100e08d5433eaaa8b3f3a87676dc
Source dataset
uspto-grants-2016_03
Patent number
US09284317B2

Reaction notes

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