Pyrazole → (Octahydro-quinolin-1-yl)-(5-pyrazol-1-yl-thiophen-3-yl)-methanone

HRID 2068647Notes

Reaction equation

HRID 2068647 reaction equation
Br[C:2]1[S:6][CH:5]=[C:4]([C:7]([N:9]2[C@@H:18]3[C@@H:13]([CH2:14][CH2:15][CH2:16][CH2:17]3)[CH2:12][CH2:11][CH2:10]2)=[O:8])[CH:3]=1.[NH:19]1[CH:23]=[CH:22][CH:21]=[N:20]1.C(=O)([O-])[O-].[K+].[K+]>COCCOC.[Cu](I)I>[N:9]1([C:7]([C:4]2[CH:3]=[C:2]([N:19]3[CH:23]=[CH:22][CH:21]=[N:20]3)[S:6][CH:5]=2)=[O:8])[CH:18]2[CH:13]([CH2:14][CH2:15][CH2:16][CH2:17]2)[CH2:12][CH2:11][CH2:10]1

Participants

6

Reactant 3

HCID 1048PyrazoleHCID 11430Potassium CarbonateHCID 86646712HCID 86646712, compound

Product 1

HCID 44227080(Octahydro-quinolin-1-yl)-(5-pyrazol-1-yl-thiophen-3-yl)-methanoneYield 21.9%

Reagents, catalysts & solvents 2

HCID 83717Copper iodideCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of cis-(5-bromo-thiophen-3-yl)-(octahydro-quinolin-1-yl)-methanone (0.095 g, 0.29 mmol) in DME (2 mL) was added N′N′-dimethylethylenediamine (0.005 g), pyrazole (0.039 g, 0.58 mmol), copper iodide (0.011 g) and potassium carbonate (0.040 g, 0.29 mmol). The reaction mixture was placed under nitrogen then sealed in a vial and heated at 120° C. for 79 hours. The solution was partitioned between DCM and water and the phases separated using a hydrophobic frit. The organic phase was evaporated and the compound was purified by chromatography on a silica cartridge eluting 0-10% methanol in DCM then re-purified on a larger cartridge using 0-3% methanol in DCM. The compound was further purified by HPLC on a C6 phenyl column, eluting with 50%-98% acetonitrile in water (0.1% formic acid). The fractions containing the desired product were evaporated to give the title compound as a colourless oil (0.02 g). LCMS m/z 316.19 [M+H]+ R.T.=10.74 min (Analytical Method 2).

Workup

  1. customthen sealed in a vial and
  2. customThe solution was partitioned between DCM and water
  3. customthe phases separated
  4. customThe organic phase was evaporated
  5. customthe compound was purified by chromatography on a silica cartridge
  6. washeluting 0-10% methanol in DCM
  7. customthen re-purified on a larger cartridge
  8. customThe compound was further purified by HPLC on a C6 phenyl column
  9. washeluting with 50%-98% acetonitrile in water (0.1% formic acid)
  10. additionThe fractions containing the desired product
  11. customwere evaporated

Sources & evidence

ORD record
ord-647ff8b96e58423792921f67560ad7f4
Source dataset
uspto-grants-2012_10
Patent number
US08299063B2

Reaction notes

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