3-piperazin-1-ylpropanamide

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2,10-dichloro-7-fluoro-10,11-dihydrodibenzo(b,f)-thiepin (2.8 g), 3-(1-piperazinyl)propionamide (3.2 g) and chloroform (10 ml) is refluxed with stirring for 8 hours. The solvent is than evaporated under reduced pressure, and the residue is extracted by shaking with a two-phase system consisting of benzene (30 ml) and a solution of methanesulfonic acid (4 g) in water (50 ml). The clear aqueous solution is separated and then made alkaline with aqueous ammonia (10 ml). The so-formed suspension of the amorphous base is diluted with ethanol (100 ml), and the mixture is briefly warmed to boiling. The resultant clear solution is then allowed to crystallize at room temperature for 6 hours. The crystalline product is separated, washed with a small amount of ethanol, and then dried in vacuo. The obtained base (2.35 g, 60% of theory) melts at 179°-182° C.; it can be purified by crystallization from ethanol to give the title compound having a m.p. of 182°-184° C. and which is identical with the product of the preceding example 1. is refluxed than evaporated under reduced pressure the residue is extracted by shaking with a two-phase system The clear aqueous solution is separated The so-formed suspension of the amorphous base is diluted with ethanol (100 ml) the mixture is briefly warmed to boiling to crystallize at room temperature for 6 hours The crystalline product is separated washed with a small amount of ethanol dried in vacuo it can be purified by crystallization from ethanol

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a manner analogous to the method described in examples 8, (4S,5R)-2-(6-tert-butyl-4-ethoxy-pyridin-3-yl)-4,5-bis-(4-chloro-phenyl)-4,5-dimethyl-4,5-dihydro-imidazole-1-carbonyl chloride (example 51) was coupled with 3-piperazin-1-yl-propionamide (Oakwood) to give the title compound. HR-MS (ES, m/z) calculated for C36H45Cl2N6O3 [(M+H)+] 679.2925, observed 679.2928.