Piperidine → HCID 86669255, compound

Participants

Reaction Conditions

Reaction Steps

(cis)-1-Acetyl-2-methyl-6-[4-(1-piperidinylmethyl)phenyl]-1,2,3,4-tetrahydro-4-quinolinamine (for a preparation see Intermediate 2) (50 mg, 0.132 mmol) was dissolved in dichloromethane (DCM) (2 mL), mixed with ethyl chloridocarbonate (0.015 mL, 0.159 mmol), and DIPEA (0.046 mL, 0.265 mmol) and stirred under nitrogen for 2.5 days. Another sample of ethyl chloridocarbonate (0.015 mL, 0.159 mmol) was added to the reaction, along with a sample of DIPEA (0.046 mL, 0.265 mmol). LCMS analysis after 73 hours reaction time indicated that the reaction had produced a side-product. The reaction was allowed to stir overnight. The reaction mixture was loaded onto a 5 g SCX-column, eluting with MeOH (70 mL) followed by 2M MeOH/NH3 (70 mL). Fractions were evaporated to dryness to give a solid which was further purified on a 12+M Biotage silica columns, eluting with cyclohexane:EtOAc (1:0 to 1:1). Product-containing fractions were evaporated to dryness to give a white solid (38 mg) that was characterised as ethyl {1-acetyl-6-[4-(chloromethyl)phenyl]-2-methyl-1,2,3,4-tetrahydro-4-quinolinyl}carbamate. Some of this material (24 mg, 0.060 mmol) was added to a solution of piperidine (0.036 mL, 0.363 mmol) mixed with acetonitrile (4 mL), along with six equivalents of potassium carbonate (60.2 mg, 0.435 mmol) and the solution was refluxed under nitrogen at 85° C. for 15 hours then cooled and loaded onto a 5 g SCX-column, eluting with MeOH (70 mL) followed by 2M MeOH/NH3 (70 mL). Product-containing fractions were evaporated to dryness to give a clear, colourless solid (35 mg). This was purified on a 12+M Biotage silica column, eluting with DCM:2M MeOH/NH3 (1:0 to 49:1). Product-containing fractions were evaporated to dryness to give a clear, colourless solid (21 mg).

Provenance & Evidence