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

HRID 79442Notes

Reaction equation

HRID 79442 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]([CH2:46][CH3:47])=[N:32][N:33]4[CH2:38][C:39]3[CH:43]=[CH:42][N:41]([CH2:44][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>O.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>[CH2:46]([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:43]=[CH:42][N:41]([CH2:44][CH3:45])[N:40]=2)[N:32]=1)[CH3:47]

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 672612817-bromo-N-(3-ethyl-1-((1-ethyl-1H-pyrazol-3-yl)methyl)-1H-indazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamideHCID 86672217water DMF CH3CN

Product 1

HCID 67259773N-(3-ethyl-1-((1-ethyl-1H-pyrazol-3-yl)methyl)-1H-indazol-4-yl)-7-(1-methyl-1H-pyrazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamideYield 61.2%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 21226129Dichloromethane methanolSolvent

Conditions

Temperature
80 °C

Procedure

A dry, 10 mL round bottom 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 (25.4 mg, 0.122 mmol), 7-bromo-N-(3-ethyl-1-((1-ethyl-1H-pyrazol-3-yl)methyl)-1H-indazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide (50 mg, 0.102 mmol), Pd(PPh3)4 (5.9 mg, 0.005 mmol), and potassium carbonate (70 mg, 0.51 mmol). To the flask was added a water:DMF:CH3CN (1:1:4.5; 0.3:0.3:1.4 mL) mixture, and the reaction mixture was degassed under nitrogen, and heated at 80° C. for 5 hours. The cooled reaction mixture was diluted with water, the resulting suspension was extracted thoroughly 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 5% MeOH-DCM as eluent to afford 30.8 mg of product as a yellow solid. MS (ES+APCI) m/z=494 (M+H) detected

Workup

  1. customA dry, 10 mL round bottom flask equipped with a reflux condenser
  2. customthe reaction mixture was degassed under nitrogen
  3. customThe cooled reaction mixture
  4. extractionthe resulting suspension was extracted thoroughly with EtOAc and DCM
  5. dry with materialthe combined organic extracts were dried over anhydrous sodium sulfate
  6. concentrationconcentrated
  7. customto afford the crude product

Sources & evidence

ORD record
ord-40f9658ebc6e4982bbce6770cd2829e5
Source dataset
uspto-grants-2014_09
Patent number
US08841455B2

Reaction notes

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