Reaction #2000142

Reaction equation

Triethylamine

1-ethynyl-4-trifluoromethoxybenzene

product

3,3-dimethyl-N-[3-(pyridin-3-yl)pyrazolo[1,5-a]pyrimidin-2-yl]butanamide

→

title compound

3,3-dimethyl-N-(3-{[4-(trifluoromethoxy)phenyl]ethynyl}pyrazolo[1,5-a]pyrimidin-2-yl)butanamide

Solvents

tetrahydrofuran

Conditions

Workup

1. 1
   OtherThe mixture was purged with a nitrogen stream for 2 minutes
2. 2
   TemperatureThe reaction mixture was cooled
3. 3
   Otherpartitioned between dichloromethane (2×50 mL) and 1.0 M sodium carbonate (100 mL)
4. 4
   DryingThe combined organic extracts were dried (sodium sulfate)
5. 5
   Filtrationfiltered
6. 6
   Concentrationconcentrated under vacuum
7. 7
   OtherThe resulting residue was purified by reverse-phase HPLC [Waters XBridge™ RP18 column, 5 μm, 30×100 mm, flow rate 40 mL/minute, 20-100% gradient of acetonitrile in buffer (0.1 M aqueous ammonium bicarbonate, adjusted to pH 10 with ammonium hydroxide)]

Procedure

Triethylamine (3 mL) was added to a mixture of bis(tri-t-butylphosphino)palladium (9.6 mg, 0.019 mmol; Strem), 1-ethynyl-4-trifluoromethoxybenzene (0.12 mL, 0.75 mmol), CuI (3.6 mg, 0.019 mmol) and the product from Example 110B (117 mg, 0.38 mmol) in anhydrous tetrahydrofuran (3 mL). The mixture was purged with a nitrogen stream for 2 minutes, and then stirred at 85° C. for 18 hours in a sealed tube. The reaction mixture was cooled and partitioned between dichloromethane (2×50 mL) and 1.0 M sodium carbonate (100 mL). The combined organic extracts were dried (sodium sulfate), filtered, and concentrated under vacuum. The resulting residue was purified by reverse-phase HPLC [Waters XBridge™ RP18 column, 5 μm, 30×100 mm, flow rate 40 mL/minute, 20-100% gradient of acetonitrile in buffer (0.1 M aqueous ammonium bicarbonate, adjusted to pH 10 with ammonium hydroxide)] to afford the title compound. 1H NMR (400 MHz, DMSO-d6) δ ppm 10.34 (s, 1H), 9.12 (dd, J=6.9, 1.7 Hz, 1H), 8.65 (dd, J=4.1, 1.7 Hz, 1H), 7.58-7.60 (m, 2H), 7.41-7.44 (m, 2H), 7.17 (dd, J=6.9, 4.1 Hz, 1H), 2.29 (s, 2H), 1.07 (s, 9H); MS (APCI) m/z 417 (M+H)+.

Source