Potassium Carbonate → 4-(8-amino-3-(4-hydroxy-1-methyl-4,5,6,7-tetrahydro-1H-indazol-4-yl)imidazo[1,5-a]pyrazin-1-yl)-N-(4-(trifluoromethyl)pyridin-2-yl)benzamide

HRID 62463Notes

Reaction equation

HRID 62463 reaction equation
[NH2:1][C:2]1[C:3]2[N:4]([C:8]([C:12]3([OH:22])[CH2:20][CH2:19][CH2:18][C:17]4[N:16]([CH3:21])[N:15]=[CH:14][C:13]3=4)=[N:9][C:10]=2Br)[CH:5]=[CH:6][N:7]=1.CC1(C)C(C)(C)OB([C:31]2[CH:49]=[CH:48][C:34]([C:35]([NH:37][C:38]3[CH:43]=[C:42]([C:44]([F:47])([F:46])[F:45])[CH:41]=[CH:40][N:39]=3)=[O:36])=[CH:33][CH:32]=2)O1.C([O-])([O-])=O.[K+].[K+].O1CCOCC1>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].O>[NH2:1][C:2]1[C:3]2[N:4]([C:8]([C:12]3([OH:22])[CH2:20][CH2:19][CH2:18][C:17]4[N:16]([CH3:21])[N:15]=[CH:14][C:13]3=4)=[N:9][C:10]=2[C:31]2[CH:49]=[CH:48][C:34]([C:35]([NH:37][C:38]3[CH:43]=[C:42]([C:44]([F:45])([F:46])[F:47])[CH:41]=[CH:40][N:39]=3)=[O:36])=[CH:33][CH:32]=2)[CH:5]=[CH:6][N:7]=1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 312751,4-DioxaneHCID 712227974-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-N-(4-(trifluoromethyl)pyridin-2-yl)benzamideHCID 712267804-(8-amino-1-bromoimidazo[1,5-a]pyrazin-3-yl)-1-methyl-4,5,6,7-tetrahydro-1H-indazol-4-ol

Product 1

HCID 769012284-(8-amino-3-(4-hydroxy-1-methyl-4,5,6,7-tetrahydro-1H-indazol-4-yl)imidazo[1,5-a]pyrazin-1-yl)-N-(4-(trifluoromethyl)pyridin-2-yl)benzamide

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolvent

Conditions

Temperature
110 °C

Procedure

The reaction mixture of 4-(8-amino-1-bromoimidazo[1,5-a]pyrazin-3-yl)-1-methyl-4,5,6,7-tetrahydro-1H-indazol-4-ol (580 mg, 1.6 mmol), 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-N-(4-(trifluoromethyl)pyridin-2-yl)benzamide (2 mmol), Pd(dppf)Cl2 (80 mg) and K2CO3 (830 mg, 6 mmol) in a mixed solvent of dioxane (15 mL) and H2O (2 mL) was stirred at 110° C. for 1.5 hrs under N2 protection. After cooling, the resulting mixture was filtered and the filtrate was evaporated under reduce pressure to dryness. The residue was purified by preparative TLC to afford 4-(8-amino-3-(4-hydroxy-1-methyl-4,5,6,7-tetrahydro-1H-indazol-4-yl)imidazo[1,5-a]pyrazin-1-yl)-N-(4-(trifluoromethyl)pyridin-2-yl)benzamide.

Workup

  1. temperatureAfter cooling
  2. filtrationthe resulting mixture was filtered
  3. customthe filtrate was evaporated
  4. customThe residue was purified by preparative TLC

Sources & evidence

ORD record
ord-835e4eb0a1434566be9252a875d3df25
Source dataset
uspto-grants-2016_09
Patent number
US09446130B2

Reaction notes

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