Reaction #71707

Reaction equation

4-({(3S)-4-[(6-iodo-3-pyridinyl)carbonyl]-3-methyl-1-piperazinyl}sulfonyl)-3-methylbenzonitrile

potassium phosphate

cyclopropylboronic acid

Tricyclohexylphosphine

→

title compound

Yield 2.4%

4-({(3S)-4-[(6-cyclopropyl-3-pyridinyl)carbonyl]-3-methyl-1-piperazinyl}sulfonyl)-3-methylbenzonitrile

Yield 2.4%

Solvents

toluene

water

Conditions

Workup

1. 1
   TemperatureThe solution was cooled
2. 2
   Concentrationconcentrated under vacuum
3. 3
   Otherto leave a pale yellow solid
4. 4
   OtherPurification by MDAP and concentration of the desired fractions

Procedure

Argon was bubbled through a solution of 4-({(3S)-4-[(6-iodo-3-pyridinyl)carbonyl]-3-methyl-1-piperazinyl}sulfonyl)-3-methylbenzonitrile (50.0 mg, 0.098 mmol) (may be prepared as described in Example 50), potassium phosphate (72.8 mg, 0.343 mmol) and cyclopropylboronic acid (25.2 mg, 0.294 mmol) in toluene (3 mL) and water (200 μl) for 30 min. Tricyclohexylphosphine (2.75 mg, 9.80 μmol) and palladium(II)acetate (1.100 mg, 4.90 μmol) were added and the resulting pale yellow solution heated at 100° C. for 2 h. LCMS had not changed from 1 min, at 45° C. The solution was cooled and concentrated under vacuum to leave a pale yellow solid. Purification by MDAP and concentration of the desired fractions gave the title compound (1.0 mg) as a clear film, and a batch of recovered 4-({(3S)-4-[(6-iodo-3-pyridinyl)carbonyl]-3-methyl-1-piperazinyl}sulfonyl)-3-methylbenzonitrile (28.2 mg) starting material.

Source