Cesium carbonate → N-{3-[4-(cyclopropylcarbamoyl)phenyl]-8-[(2-methylpropyl)amino]imidazo[1,2-a]pyrazin-6-yl}pyridine-2-carboxamide

HRID 925602Notes

Reaction equation

HRID 925602 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.[N:28]1[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=1[C:34]([NH2:36])=[O:35].C(=O)([O-])[O-].[Cs+].[Cs+].CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1>C1(C)C=CC=CC=1.C1(C=CC(=O)C=CC2C=CC=CC=2)C=CC=CC=1.[Pd]>[CH:18]1([NH:17][C:15]([C:14]2[CH:21]=[CH:22][C:11]([C:8]3[N:6]4[CH:7]=[C:2]([NH:36][C:34]([C:29]5[CH:30]=[CH:31][CH:32]=[CH:33][N:28]=5)=[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)=[O:16])[CH2:20][CH2:19]1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 150702-PyridinecarboxamideHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 509145924-(6-Bromo-8-(isobutylamino)imidazo[1,2-a]pyrazin-3-yl)-N-cyclopropylbenzamide

Product 1

HCID 57404790N-{3-[4-(cyclopropylcarbamoyl)phenyl]-8-[(2-methylpropyl)amino]imidazo[1,2-a]pyrazin-6-yl}pyridine-2-carboxamideYield 29.6%

Reagents, catalysts & solvents 2

HCID 72499888Dibenzalacetone palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
140 °C

Procedure

To a solution of 100 mg (0.23 mmol) 4-{6-bromo-8-[(2-methylpropyl)amino]imidazo[1,2-a]pyrazin-3-yl}-N-cyclopropylbenzamide in 2 mL toluene were added 88 mg (0.7 mmol) pyridine-2-carboxamide, 76 mg (0.23 mmol) caesium carbonate, 8.4 mg (0.01 mmol) 1E,4E)-1,5-diphenylpenta-1,4-dien-3-one-palladium (3:2) and 10.8 mg (0.02 mmol) (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphane) and the mixture was heated at 140° C. for 2 h in a microwave tube. The mixture was filtered and purified by HPLC to yield 32 mg (28%) of the title compound. UPLC-MS: RT=1.32 min; m/z (ES+) 470.5 [MH+]; required MW=469.5. 1H-NMR (300 MHz, d6-DMSO): δ=9.88 (1H, s), 8.76 (1H, s), 8.73 (1H, d), 8.56 (1H, d), 8.13-8.04 (2H, m), 7.99 (2H, d), 7.88 (1H, t), 7.76 (1H, s), 7.72 (1H, d), 7.69 (1H, m), 3.31 (2H, t), 2.87 (1H, m), 2.06 (1H, m), 0.92 (2H, d), 0.69 (2H, m), 0.55 (2H, m) ppm.

Workup

  1. filtrationThe mixture was filtered
  2. custompurified by HPLC

Sources & evidence

ORD record
ord-3cc4eaebbc4d45479b4d4bb88f2ecf73
Source dataset
uspto-grants-2016_03
Patent number
US09284317B2

Reaction notes

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