Bromide ion → {1-[4-(3-Phenyl-7-pyrazol-1-yl-imidazo[1,2-a]pyridin-2-yl)-phenyl]-cyclobutyl}-carbamic acid tert-butyl ester

HRID 872338Notes

Reaction equation

HRID 872338 reaction equation
[C:1]([O:5][C:6](=[O:34])[NH:7][C:8]1([C:12]2[CH:17]=[CH:16][C:15]([C:18]3[N:19]=[C:20]4[CH:25]=[C:24](Br)[CH:23]=[CH:22][N:21]4[C:27]=3[C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)=[CH:14][CH:13]=2)[CH2:11][CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].[NH:35]1[CH:39]=[CH:38][CH:37]=[N:36]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].C(N)CN.[Br-]>O1CCOCC1.[Cu]I>[C:1]([O:5][C:6](=[O:34])[NH:7][C:8]1([C:12]2[CH:17]=[CH:16][C:15]([C:18]3[N:19]=[C:20]4[CH:25]=[C:24]([N:35]5[CH:39]=[CH:38][CH:37]=[N:36]5)[CH:23]=[CH:22][N:21]4[C:27]=3[C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)=[CH:14][CH:13]=2)[CH2:11][CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2]

Participants

8

Reactant 5

HCID 259Bromide ionHCID 1048PyrazoleHCID 3301EthylenediamineHCID 62657Potassium Phosphate, TribasicHCID 66665545{1-[4-(7-Bromo-3-phenyl-imidazo[1,2-a]pyridin-2-yl)-phenyl]-cyclobutyl}-carbamic acid tert-butyl ester

Product 1

HCID 66665928{1-[4-(3-Phenyl-7-pyrazol-1-yl-imidazo[1,2-a]pyridin-2-yl)-phenyl]-cyclobutyl}-carbamic acid tert-butyl esterYield 89.9%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of {1-[4-(7-bromo-3-phenyl-imidazo[1,2-a]pyridin-2-yl)-phenyl]-cyclobutyl}-carbamic acid tert-butyl ester (230 mg, 0.44 mmol), pyrazole (39 mg, 0.58 mmol), copper (I) iodide (8.5 mg, 0.044 mmol), potassium phosphate (186 mg, 0.88 mmol) and ethylene diamine (3 μL, 0.044 mmol) in dioxane (2.4 mL) was degassed, placed under an argon atmosphere and heated at 110° C. for 5 hours. On cooling, the reaction was partitioned between aqueous sodium hydrogen carbonate solution and DCM and the organic phase was washed with brine, dried and concentrated in vacuo to give the crude title compound (100 mg). The reaction was repeated using a further 150 mg of the bromide intermediate to give a further batch of the crude title compound (140 mg). Purification by chromotagraphy gave the title compound (200 mg), which was used in the next step without further purification.

Workup

  1. customwas degassed
  2. temperatureOn cooling
  3. customthe reaction was partitioned between aqueous sodium hydrogen carbonate solution and DCM
  4. washthe organic phase was washed with brine
  5. customdried
  6. concentrationconcentrated in vacuo
  7. customto give the crude title compound (100 mg)
  8. customto give a further batch of the crude title compound (140 mg)
  9. customPurification by chromotagraphy

Sources & evidence

ORD record
ord-c29f57e8bd72438498f91a650b1e0420
Source dataset
uspto-grants-2015_03
Patent number
US08975265B2

Reaction notes

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