Methanol → N-(3-ethyl-1-((1-(4-methoxybenzyl)-1H-pyrazol-4-yl)methyl)-1H-indazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide

HRID 79313Notes

Reaction equation

HRID 79313 reaction equation
I[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][C:9]=2[NH:11][C:12]([C:14]2[N:18]3[CH:19]=[CH:20][CH:21]=[CH:22][C:17]3=[N:16][CH:15]=2)=[O:13])[N:4]([CH2:23][C:24]2[CH:25]=[N:26][N:27]([CH2:29][C:30]3[CH:35]=[CH:34][C:33]([O:36][CH3:37])=[CH:32][CH:31]=3)[CH:28]=2)[N:3]=1.B(O)(O)O.F[C:43]([K])=[C:44](F)F.C(N(CC)CC)C.CO>C1COCC1.CC(O)C.[OH-].[OH-].[Pd+2]>[CH2:43]([C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][C:9]=2[NH:11][C:12]([C:14]2[N:18]3[CH:19]=[CH:20][CH:21]=[CH:22][C:17]3=[N:16][CH:15]=2)=[O:13])[N:4]([CH2:23][C:24]2[CH:25]=[N:26][N:27]([CH2:29][C:30]3[CH:35]=[CH:34][C:33]([O:36][CH3:37])=[CH:32][CH:31]=3)[CH:28]=2)[N:3]=1)[CH3:44]

Participants

7

Reactant 4

HCID 887MethanolHCID 8471TriethylamineHCID 67259250N-(3-iodo-1-((1-(4-methoxybenzyl)-1H-pyrazol-4-yl)methyl)-1H-indazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamideHCID 178506051HCID 178506051, compound

Product 1

HCID 67260032N-(3-ethyl-1-((1-(4-methoxybenzyl)-1H-pyrazol-4-yl)methyl)-1H-indazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamideYield 64.6%

Reagents, catalysts & solvents 2

HCID 9942167Palladium hydroxideCatalystHCID 22597222Tetrahydrofuran 2-propanolSolvent

Conditions

Temperature
86 °C

Procedure

To N-(3-iodo-1-((1-(4-methoxybenzyl)-1H-pyrazol-4-yl)methyl)-1H-indazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide (0.59 g, 0.98 mmol) in THF/IPA (1 mL/3 mL) was added trifluorovinylpotassium borate (0.20 g, 1.5 mmol), triethylamine (0.20 g, 2.0 mmol) and 1,1′-Bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (0.080 g, 0.098 mmol). The reaction mixture was heated at 86° C. and stirred for 5 hours. The reaction mixture was cooled to ambient temperature, concentrated under reduced pressure, and triturated with Et2O (30 mL) to give crude vinyl product, to which palladium hydroxide on carbon (20% wt, 0.27 mmol) and MeOH (20 mL) was added. The system was purged with N2 three times and a H2 balloon was applied to the system for 2 hours. The reaction mixture was filtered through Celite, washed with MeOH (20 mL), and concentrated to give the product (0.32 g). MS (ES+APCI) m/z=506 (M+H).

Workup

  1. temperatureThe reaction mixture was cooled to ambient temperature
  2. concentrationconcentrated under reduced pressure
  3. customtriturated with Et2O (30 mL)
  4. customto give crude vinyl product
  5. customThe system was purged with N2 three times
  6. waita H2 balloon was applied to the system for 2 hours
  7. filtrationThe reaction mixture was filtered through Celite
  8. washwashed with MeOH (20 mL)
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-b987d732b629444da24cc58412887f6f
Source dataset
uspto-grants-2014_09
Patent number
US08841455B2

Reaction notes

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