Triethylamine → 3-(4-Fluorophenyl)-imidazo[1,5-a]pyridine-8-carboxylic acid 3-trifluoromethyl-benzylamide

HRID 1423029Notes

Reaction equation

HRID 1423029 reaction equation
Br[C:2]1[C:3]2[N:4]([C:8]([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=3)=[N:9][CH:10]=2)[CH:5]=[CH:6][CH:7]=1.CC[N:20]([CH2:23][CH3:24])[CH2:21]C.[F:25][C:26]([F:36])([F:35])[C:27]1[CH:28]=C([CH:32]=[CH:33][CH:34]=1)CN.[C]=[O:38]>C1(C)C=CC=CC=1.[Cl-].[NH4+].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.[Fe+2]>[F:25][C:26]([F:36])([F:35])[C:27]1[CH:28]=[C:24]([CH:32]=[CH:33][CH:34]=1)[CH2:23][NH:20][C:21]([C:2]1[C:3]2[N:4]([C:8]([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=3)=[N:9][CH:10]=2)[CH:5]=[CH:6][CH:7]=1)=[O:38]

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 759623-(Trifluoromethyl)benzylamineHCID 671955508-Bromo-3-(4-fluorophenyl)-imidazo[1,5-a]pyridineHCID 178418416HCID 178418416, compound

Product 1

HCID 529356403-(4-Fluorophenyl)-imidazo[1,5-a]pyridine-8-carboxylic acid 3-trifluoromethyl-benzylamide

Reagents, catalysts & solvents 3

HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 1140TolueneSolventHCID 25517Ammonium ChlorideSolvent

Conditions

Temperature
140 °C

Procedure

A mixture of 8-bromo-3-(4-fluorophenyl)-imidazo[1,5-a]pyridine (0.100 g, 0.344 mmol), Et3N (95.0 μL, 0.683 mmol), 3-(trifluoromethyl)benzylamine (89.0 μL, 0.621 mmol), Pd[PhCN]2Cl2 (5.0 mg, 0.013 mmol), and dppf (21 mg, 0.038 mmol) in degassed toluene (10 mL) is placed in a pressure reactor. The stirred mixture is placed under 15 bars of carbon monoxide and warmed at 140° C. After 3 hours, the pressure reactor is cooled to room temperature, returned to atmospheric pressure and opened. The reaction mixture is diluted with saturated aqueous ammonium chloride (10 mL) and extracted with EtOAc (3×10 mL). The combined organic layers are washed with saturated aqueous ammonium chloride (3×10 mL), brine (10 mL), dried over magnesium sulfate, filtered and concentrated. The residue is purified by silica gel chromatography eluting with a gradient of 0-50% EtOAc in dichloromethane. The resulting solid is triturated with ether-hexanes to afford the title compound.

Workup

  1. customis placed in a pressure reactor
  2. temperaturethe pressure reactor is cooled to room temperature
  3. extractionextracted with EtOAc (3×10 mL)
  4. washThe combined organic layers are washed with saturated aqueous ammonium chloride (3×10 mL), brine (10 mL)
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue is purified by silica gel chromatography
  9. washeluting with a gradient of 0-50% EtOAc in dichloromethane
  10. customThe resulting solid is triturated with ether-hexanes

Sources & evidence

ORD record
ord-ed940bd698bc4d40be68049441a0a93b
Source dataset
uspto-grants-2015_01
Patent number
US08927550B2

Reaction notes

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