Potassium Carbonate → N-(3-ethyl-1-((6-methylpyridin-2-yl)methyl)-1H-indazol-4-yl)-7-(5,6,7,8-tetrahydroimidazo[1,2-a]pyrazin-3-yl)imidazo[1,2-a]pyridine-3-carboxamide

HRID 79382

Reaction equation

HRID 79382 reaction equation
Br[C:2]1[CH:7]=[CH:6][N:5]2[C:8]([C:11]([NH:13][C:14]3[CH:22]=[CH:21][CH:20]=[C:19]4[C:15]=3[C:16]([CH2:31][CH3:32])=[N:17][N:18]4[CH2:23][C:24]3[CH:29]=[CH:28][CH:27]=[C:26]([CH3:30])[N:25]=3)=[O:12])=[CH:9][N:10]=[C:4]2[CH:3]=1.[N:33]1[CH:34]=[CH:35][N:36]2[CH2:41][CH2:40][N:39](C(OC(C)(C)C)=O)[CH2:38][C:37]=12.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C([O-])(=O)C.C([O-])(=O)C.[Pd+2]>[CH2:31]([C:16]1[C:15]2[C:19](=[CH:20][CH:21]=[CH:22][C:14]=2[NH:13][C:11]([C:8]2[N:5]3[CH:6]=[CH:7][C:2]([C:35]4[N:36]5[CH2:41][CH2:40][NH:39][CH2:38][C:37]5=[N:33][CH:34]=4)=[CH:3][C:4]3=[N:10][CH:9]=2)=[O:12])[N:18]([CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[C:26]([CH3:30])[N:25]=2)[N:17]=1)[CH3:32]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 21955306tert-Butyl 5,6-dihydroimidazo(1,2-a)pyrazine-7(8H)-carboxylateHCID 672595577-Bromo-N-(3-ethyl-1-((6-methylpyridin-2-yl)methyl)-1H-indazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide

Product 1

HCID 53262090N-(3-ethyl-1-((6-methylpyridin-2-yl)methyl)-1H-indazol-4-yl)-7-(5,6,7,8-tetrahydroimidazo[1,2-a]pyrazin-3-yl)imidazo[1,2-a]pyridine-3-carboxamideYield 26.3%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
140 °C

Procedure

7-Bromo-N-(3-ethyl-1-((6-methylpyridin-2-yl)methyl)-1H-indazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide (prepared as in Example 127, Step A; 50 mg, 0.10 mmol) in DMF (4 mL) was added tert-butyl 5,6-dihydroimidazo[1,2-a]pyrazine-7(8H)-carboxylate (68 mg, 0.31 mmol), Pd(PPh3)4 (12 mg, 0.01 mmol), palladium diacetate (2.3 mg, 0.010 mmol) and K2CO3 (42 mg, 0.31 mmol). The reaction mixture was purged with argon and the reaction vial was sealed and the mixture was heated to 140° C. for 3 hours. The mixture was cooled to ambient temperature and diluted with DCM (20 mL). The solution was washed with H2O, dried (Na2SO4) and concentrated under reduced pressure. The residue was purified by silica gel chromatography (DCM/MeOH/NH4OH 10:1:0.1) to provide the final product (14 mg). MS (ES+APCI) m/z=532 (M+H).

Workup

  1. customThe reaction mixture was purged with argon
  2. customthe reaction vial was sealed
  3. temperatureThe mixture was cooled to ambient temperature
  4. additiondiluted with DCM (20 mL)
  5. washThe solution was washed with H2O
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by silica gel chromatography (DCM/MeOH/NH4OH 10:1:0.1)

Sources & evidence

ORD record
ord-50c00976280348d0b5e801d60b2b650b
Source dataset
uspto-grants-2014_09
Patent number
US08841455B2

Linked notes

Loading…