Reaction #962245

Reaction equation

(4-(4-fluorobenzyl)piperazin-1-yl)(6-bromopyridin-3-yl)methanone

4-benzyloxyphenylboronic acid

potassium phosphate

S-Phos

→

Compound 17

(4-(4-fluorobenzyl)piperazin-1-yl)(6-(4-(benzyloxy)phenyl)pyridin-3-yl)methanone

Solvents

1-butanol water

Conditions

Workup

1. 1
   Otherpurge of the reaction mixture with argon
2. 2
   Otherthe reaction vessel was sealed
3. 3
   FiltrationThe reaction mixture was filtered through Celite®
4. 4
   Washeluting with 5% MeOH—CH2Cl2
5. 5
   Otherpurified by RP-HPLC

Procedure

To a mixture of (4-(4-fluorobenzyl)piperazin-1-yl)(6-bromopyridin-3-yl)methanone (0.048 g, 0.13 mmol, 1.0 eq), 4-benzyloxyphenylboronic acid (0.040 g, 0.18 mmol, 1.4 eq), potassium phosphate (0.053 g, 0.25 mmol, 1.9 eq), S-Phos (0.006 g, 0.01 mmol, 0.1 eq), and tris(dibenzylideneacetone)dipalladium(0) (0.012 g, 0.01 mmol, 0.01 eq) was added 1-butanol-water (1.25 mL, 4:1). Following a 5 minute purge of the reaction mixture with argon, the reaction vessel was sealed and heated at 100° C. for 10 hours. The reaction mixture was filtered through Celite®, eluting with 5% MeOH—CH2Cl2 and purified by RP-HPLC to provide Compound 17. 1H nmr (D6-DMSO) δ 8.61 (1H, s), 8.06 (2H, d, J 9.0 Hz), 7.95 (1H, d, J 8.0 Hz), 7.83 (1H, dd, J 8.0, 2.0 Hz), 7.48-7.30 (7H, m), 7.16-7.10 (4H, m), 5.16 (2H, s), 3.61 (2H, m), 3.48 (2H, s), 3.37 (2H, m), 2.38 (4H, m); m/z: 483 [M+H]+.

Source