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

HRID 706625Notes

Reaction equation

HRID 706625 reaction equation
[CH3:1][N:2]1[CH:6]=[C:5](B2OC(C)(C)C(C)(C)O2)[CH:4]=[N:3]1.Br[C:17]1[CH:22]=[CH:21][N:20]2[C:23]([C:26]([NH:28][C:29]3[CH:37]=[CH:36][CH:35]=[C:34]4[C:30]=3[C:31]([CH3:46])=[N:32][N:33]4[CH2:38][C:39]3[CH:44]=[CH:43][CH:42]=[C:41]([CH3:45])[N:40]=3)=[O:27])=[CH:24][N:25]=[C:19]2[CH:18]=1.C(=O)([O-])[O-].[K+].[K+].O.CN(C=O)C.CC#N>CO.C(Cl)Cl.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>[CH3:46][C:31]1[C:30]2[C:34](=[CH:35][CH:36]=[CH:37][C:29]=2[NH:28][C:26]([C:23]2[N:20]3[CH:21]=[CH:22][C:17]([C:5]4[CH:4]=[N:3][N:2]([CH3:1])[CH:6]=4)=[CH:18][C:19]3=[N:25][CH:24]=2)=[O:27])[N:33]([CH2:38][C:39]2[CH:44]=[CH:43][CH:42]=[C:41]([CH3:45])[N:40]=2)[N:32]=1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 679764107-bromo-N-(3-methyl-1-((6-methylpyridin-2-yl)methyl)-1H-indazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamideHCID 86672217water DMF CH3CN

Product 1

HCID 57387151N-(3-methyl-1-((6-methylpyridin-2-yl)methyl)-1H-indazol-4-yl)-7-(1-methyl-1H-pyrazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamideYield 42.3%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 21226129Dichloromethane methanolSolvent

Conditions

Temperature
80 °C

Procedure

A dried flask equipped with a reflux condenser and a nitrogen line was charged with 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (14.4 mg, 0.069 mmol), 7-bromo-N-(3-methyl-1-((6-methylpyridin-2-yl)methyl)-1H-indazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide (Example 50, Steps A-B; 30 mg, 0.063 mmol), Pd(PPh3)4 (3.7 mg, 0.003 mmol), and potassium carbonate (44 mg, 0.32 mmol). To the flask was added a water:DMF:CH3CN (1:1:4.5; 0.16:0.16:1.0 mL) mixture, and the reaction mixture was degassed under nitrogen and heated at 80° C. for 5 hours. The reaction mixture was cooled and diluted with water. The resulting suspension was extracted with EtOAc and DCM. The combined organic extracts were dried over anhydrous sodium sulfate and concentrated to afford the crude product. The crude product was subjected to preparative thin-layer chromatography on silica with 8% MeOH/DCM as eluent to afford 12.7 mg of product as a yellow solid. MS (ES+APCI) m/z=477 (M+H) detected.

Workup

  1. customA dried flask equipped with a reflux condenser
  2. customthe reaction mixture was degassed under nitrogen
  3. temperatureThe reaction mixture was cooled
  4. additiondiluted with water
  5. extractionThe resulting suspension was extracted with EtOAc and DCM
  6. dry with materialThe combined organic extracts were dried over anhydrous sodium sulfate
  7. concentrationconcentrated
  8. customto afford the crude product

Sources & evidence

ORD record
ord-ccb350cb7dab48d98954ddef141818f5
Source dataset
uspto-grants-2015_11
Patent number
US09174981B2

Reaction notes

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