Piperidine → HCID 86669255, compound

HRID 2366917Notes

Reaction equation

HRID 2366917 reaction equation
[C:1]([N:4]1[C:13]2[C:8](=[CH:9][C:10]([C:14]3[CH:19]=[CH:18][C:17]([CH2:20]Cl)=[CH:16][CH:15]=3)=[CH:11][CH:12]=2)[CH:7]([NH:22][C:23](=[O:27])[O:24][CH2:25][CH3:26])[CH2:6][CH:5]1[CH3:28])(=[O:3])[CH3:2].[NH:29]1[CH2:34][CH2:33][CH2:32][CH2:31][CH2:30]1.C(=O)([O-])[O-].[K+].[K+]>C(#N)C>[C:1]([N:4]1[C:13]2[C:8](=[CH:9][C:10]([C:14]3[CH:19]=[CH:18][C:17]([CH2:20][N:29]4[CH2:34][CH2:33][CH2:32][CH2:31][CH2:30]4)=[CH:16][CH:15]=3)=[CH:11][CH:12]=2)[C@H:7]([NH:22][C:23](=[O:27])[O:24][CH2:25][CH3:26])[CH2:6][C@@H:5]1[CH3:28])(=[O:3])[CH3:2]

Participants

5

Reactant 3

HCID 8082PiperidineHCID 11430Potassium CarbonateHCID 86669256HCID 86669256, compound

Product 1

HCID 86669255HCID 86669255, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
85 °C

Procedure

(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).

Workup

  1. temperaturethen cooled
  2. washeluting with MeOH (70 mL)
  3. customProduct-containing fractions were evaporated to dryness

Sources & evidence

ORD record
ord-77670f468b2d4ed6bd8902ed6ac37c31
Source dataset
uspto-grants-2014_04
Patent number
US08697725B2

Reaction notes

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