Sodium Carbonate → 4-{2-[4-(1-Tert-butoxycarbonylamino-cyclobutyl)-phenyl]-3-phenyl-imidazo[1,2-a]pyridin-7-yl}-pyrazole-1-carboxylic acid tert-butyl ester

HRID 872319Notes

Reaction equation

HRID 872319 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].[C:35]([O:39][C:40]([N:42]1[CH:46]=[C:45](B(O)O)[CH:44]=[N:43]1)=[O:41])([CH3:38])([CH3:37])[CH3:36].C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.O.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].Cl[Pd]Cl>[C:35]([O:39][C:40]([N:42]1[CH:46]=[C:45]([C:24]2[CH:23]=[CH:22][N:21]3[C:27]([C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=4)=[C:18]([C:15]4[CH:16]=[CH:17][C:12]([C:8]5([NH:7][C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:34])[CH2:11][CH2:10][CH2:9]5)=[CH:13][CH:14]=4)[N:19]=[C:20]3[CH:25]=2)[CH:44]=[N:43]1)=[O:41])([CH3:38])([CH3:36])[CH3:37]

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 441186751-tert-Butoxycarbonyl-1H-pyrazole-4-boronic acidHCID 66665545{1-[4-(7-Bromo-3-phenyl-imidazo[1,2-a]pyridin-2-yl)-phenyl]-cyclobutyl}-carbamic acid tert-butyl ester

Product 1

HCID 666657094-{2-[4-(1-Tert-butoxycarbonylamino-cyclobutyl)-phenyl]-3-phenyl-imidazo[1,2-a]pyridin-7-yl}-pyrazole-1-carboxylic acid tert-butyl esterYield 104.4%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
105 °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 (150 mg), [1-(tert-butoxycarbonyl)-1H-pyrazol-4-yl]boronic acid (123 mg), 1,1′-bis(diphenylphosphino)ferrocene-dichloropalladium(II) (24 mg) and sodium carbonate (92 mg) in dioxane (3.1 mL) and water (0.4 mL) was degassed, placed under an argon atmosphere and heated at 105° C. under microwave irradiation for 30 minutes. On cooling, a further portion of catalyst was added (24 mg) and the mixture heated for a further 30 minutes under microwave irradiation. On cooling, the reaction was partitioned between aqueous ammonium chloride solution and DCM and the organic phase washed with brine, dried and concentrated in vacuo to give the crude title compound (183 mg) which was used in the next step (deprotection of both Boc groups under the standard conditions given in Example 1.0) without further purification.

Workup

  1. customwas degassed
  2. temperatureOn cooling
  3. additiona further portion of catalyst was added (24 mg)
  4. temperaturethe mixture heated for a further 30 minutes under microwave irradiation
  5. temperatureOn cooling
  6. customthe reaction was partitioned between aqueous ammonium chloride solution and DCM
  7. washthe organic phase washed with brine
  8. customdried
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-1098d0592ea24393842c23ba07c5aa30
Source dataset
uspto-grants-2015_03
Patent number
US08975265B2

Reaction notes

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