Pyrazole → tert-butyl (1-{4-[3-phenyl-6-(1H-pyrazol-1-yl)imidazo[1,2-a]pyridin-2-yl]phenyl}cyclobutyl)carbamate

HRID 872339Notes

Reaction equation

HRID 872339 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)=[C:9]([C:11]3[CH:16]=[CH:15][C:14]([C:17]4([NH:21][C:22](=[O:28])[O:23][C:24]([CH3:27])([CH3:26])[CH3:25])[CH2:20][CH2:19][CH2:18]4)=[CH:13][CH:12]=3)[N:10]=2)[CH:7]=1.[NH:35]1[CH:39]=[CH:38][CH:37]=[N:36]1.C(=O)([O-])[O-].[K+].[K+].N1C2C(=CC=CC=2O)C=CC=1>CS(C)=O.[Cu]I>[C:29]1([C:8]2[N:6]3[CH:7]=[C:2]([N:35]4[CH:39]=[CH:38][CH:37]=[N:36]4)[CH:3]=[CH:4][C:5]3=[N:10][C:9]=2[C:11]2[CH:12]=[CH:13][C:14]([C:17]3([NH:21][C:22](=[O:28])[O:23][C:24]([CH3:25])([CH3:26])[CH3:27])[CH2:18][CH2:19][CH2:20]3)=[CH:15][CH:16]=2)[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=1

Participants

7

Reactant 4

HCID 1048PyrazoleHCID 19238-HydroxyquinolineHCID 11430Potassium CarbonateHCID 66665495Tert-butyl {1-[4-(6-bromo-3-phenylimidazo[1,2-a]pyridin-2-yl)phenyl]cyclobutyl}carbamate

Product 1

HCID 68084186tert-butyl (1-{4-[3-phenyl-6-(1H-pyrazol-1-yl)imidazo[1,2-a]pyridin-2-yl]phenyl}cyclobutyl)carbamateYield 8.9%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
150 °C

Procedure

A mixture of tert-butyl {1-[4-(6-bromo-3-phenylimidazo[1,2-a]pyridin-2-yl)phenyl]cyclobutyl}carbamate (see Int 4-18, 230 mg, 0.443 mmol), copper(I) iodide (12.6 mg, 0.07 mmol), 1H-pyrazole (36.5 mg, 0.537 mmol), potassium carbonate (36.5 mg, 0.537 mmol) and quinolin-8-ol (9.73 mg, 0.007 mmol) in 0.6 ml DMSO was heated to 150° C. for 7 h under argon atmosphere. The mixture was triturated with 10% ammonium hydroxide solution and charcoal. After filtration through Celite the filter pad was washed with ethyl acetate. The combined solutions were washed with brine and filtered through a silicone filter. The volatile compounds were removed in vacuo. The crude material was purified by reverse phase HPLC chromatography (Chromatorex RP C-18 10_m; 125*30 mm, acetonitrile/water 30/70->acetonitrile/water 100/0) to give 20 mg of the title compound (9 (Y0 overall yield).

Workup

  1. customThe mixture was triturated with 10% ammonium hydroxide solution and charcoal
  2. filtrationAfter filtration through Celite the filter pad
  3. washwas washed with ethyl acetate
  4. washThe combined solutions were washed with brine
  5. filtrationfiltered through a silicone
  6. filtrationfilter
  7. customThe volatile compounds were removed in vacuo
  8. customThe crude material was purified by reverse phase HPLC chromatography (Chromatorex RP C-18 10_m; 125*30 mm, acetonitrile/water 30/70->acetonitrile/water 100/0)

Sources & evidence

ORD record
ord-dc0a58a19c1949238db6a00af0269a56
Source dataset
uspto-grants-2015_03
Patent number
US08975265B2

Reaction notes

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