Dichloromethane → HCID 19921682, compound

Participants

Reaction Steps

To a suspension of NaH (60% in oil, 0.020 g, 0.5 mmol) in 10 mL of dry THF was added a suspension of 3-[3-[4-(5-methoxy-4-pyrimidyl)-1-piperazinyl]propyl]-5-hydroxyindole (0.183 g, 0.5 mmol) in 20 mL of THF, at room temperature under Ar. After 30 min gas evolution had ceased and a clear solution was obtained. To this solution was added a solution of chloroacetonitrile (35 μL, 0.55 mmol) in 5 mL of dry THF, and the mixture was stirred at room temperature for 2 h and then refluxed for 11/2 h. The cooled mixture was diluted with CH2Cl2 , washed (water, brine), dried (Na2SO4) and evaporated to give a foam. Column chromatography (SiO2 /CH2Cl2 -MeOH, 95:5; then CH2Cl2 -MeOH-NH4OH, 95:4.5;0.5) afforded the title compound (0.150 g, 75%) as a foam. This material was treated with excess methanolic HCl and the solution was evaporated to give a glass. Trituration with MeOH-EtOH (1:9) gave the hydrochloride (0.110 g) as an off-white solid, m.p. 198°-200° C. (dec): IR (KBr) 3400, 3220, 1630 cm-1 ; 1H NMR (DMSO-d6, 200 MHz) δ11.39 (br s, 1H), 10.87 (br s, 1H), 8.61 (s, 1H), 8.20 (s, 1H), 7.30 (d, J=8.8 Hz, 1H), 7.24 (d, J=2.4 Hz, 1H), 7.22 (d, J=2.0 Hz, 1H), 6.83 (dd, J=8.7, 2.4 Hz, 1H), 5.16 (s, 2H), 4.90-4.83 (m, 2H), 3.90 (s, 3H), 3.70-3.36 (m, 4H), 3.13 (br s, 4H), 2.75 (m, 2H), 2.12 (m, 2H). Anal. Calcd. for C22H26N6O2.2.5 HCl.0.3 C2H6O: C,53.07; H, 5.97; N, 16.43. Found; C, 53.26; H, 5.70; N, 16.11.

Provenance & Evidence