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

HRID 62480Notes

Reaction equation

HRID 62480 reaction equation
Br[C:2]1[N:3]=[C:4]([CH:12]2[CH2:17][CH2:16][N:15]3[C:18]([C:21]([F:24])([F:23])[F:22])=[N:19][N:20]=[C:14]3[CH2:13]2)[N:5]2[CH:10]=[CH:9][N:8]=[C:7]([NH2:11])[C:6]=12.CC1(C)C(C)(C)OB([C:33]2[CH:51]=[CH:50][C:36]([C:37]([NH:39][C:40]3[CH:45]=[C:44]([C:46]([F:49])([F:48])[F:47])[CH:43]=[CH:42][N:41]=3)=[O:38])=[CH:35][CH:34]=2)O1.C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.O.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]>[NH2:11][C:7]1[C:6]2[N:5]([C:4]([CH:12]3[CH2:17][CH2:16][N:15]4[C:18]([C:21]([F:24])([F:23])[F:22])=[N:19][N:20]=[C:14]4[CH2:13]3)=[N:3][C:2]=2[C:33]2[CH:34]=[CH:35][C:36]([C:37]([NH:39][C:40]3[CH:45]=[C:44]([C:46]([F:47])([F:48])[F:49])[CH:43]=[CH:42][N:41]=3)=[O:38])=[CH:50][CH:51]=2)[CH:10]=[CH:9][N:8]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 712227974-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-N-(4-(trifluoromethyl)pyridin-2-yl)benzamideHCID 90304106HCID 90304106, compound

Product 1

HCID 903041264-(8-amino-3-(3-(trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyridin-7-yl)imidazo[1,5-a]pyrazin-1-yl)-N-(4-(trifluoromethyl)pyridin-2-yl)benzamideYield 54.8%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 218864351,4-Dioxane--water (1/1)Solvent

Conditions

Temperature
90 °C

Procedure

The mixture of 1-bromo-3-(3-(trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyridine-7-yl)imidazo[1,5-a]pyrazin-8-amine (200 mg, 0.497 mmol), 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-N-(4-(trifluoromethyl)pyridin-2-yl)benzamide (194.54 mg, 0.497 mmol), Pd(dppf)Cl2 (18.3 mg, 0.025 mmol) and K2CO3 (137.26 mg, 0.995 mmol) in dioxane/H2O (5 mL/0.5 mL) was stirred at 90° C. for 2 h under nitrogen atmosphere. Remove the solvent in vacuo. The mixture was treated with ethyl acetate and water, the organic layer was separated, dried over sodium sulfate, filtered and the filtrate was concentrated. The residue was purified by preparative HPLC separation to give 4-(8-amino-3-(3-(trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyridin-7-yl)imidazo[1,5-a]pyrazin-1-yl)-N-(4-(trifluoromethyl)pyridin-2-yl)benzamide (0.16 g, yield 50%).

Workup

  1. customRemove the solvent in vacuo
  2. additionThe mixture was treated with ethyl acetate and water
  3. customthe organic layer was separated
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationthe filtrate was concentrated
  7. customThe residue was purified by preparative HPLC separation

Sources & evidence

ORD record
ord-9b8f6b561d1f47a4ae5c5e7ae44cb8f0
Source dataset
uspto-grants-2016_09
Patent number
US09446130B2

Reaction notes

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