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

HRID 706736Notes

Reaction equation

HRID 706736 reaction equation
CC1(C)C(C)(C)OB([C:9]2[CH:10]=[N:11][N:12](C(OC(C)(C)C)=O)[CH:13]=2)O1.[CH2:22]([N:29]1[C:37]2[C:32](=[C:33]([NH:38][C:39]([C:41]3[N:45]4[CH:46]=[CH:47][C:48](Br)=[CH:49][C:44]4=[N:43][CH:42]=3)=[O:40])[CH:34]=[CH:35][CH:36]=2)[CH:31]=[N:30]1)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=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>[CH2:22]([N:29]1[C:37]2[C:32](=[C:33]([NH:38][C:39]([C:41]3[N:45]4[CH:46]=[CH:47][C:48]([C:9]5[CH:10]=[N:11][NH:12][CH:13]=5)=[CH:49][C:44]4=[N:43][CH:42]=3)=[O:40])[CH:34]=[CH:35][CH:36]=2)[CH:31]=[N:30]1)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 16217654tert-butyl 4-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylateHCID 67976233N-(1-benzyl-1H-indazol-4-yl)-7-bromoimidazo[1,2-a]pyridine-3-carboxamideHCID 86672217water DMF CH3CN

Product 1

HCID 86699348N-(1-benzyl-1H-indazol-4-yl)-7-(1H-pyrazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamideYield 61.7%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 21226129Dichloromethane methanolSolvent

Conditions

Temperature
80 °C

Procedure

A dried round bottom flask equipped with a reflux condenser and a nitrogen line was charged with tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylate (16.7 mg, 0.057 mmol), N-(1-benzyl-1H-indazol-4-yl)-7-bromoimidazo[1,2-a]pyridine-3-carboxamide (23 mg, 0.052 mmol), Pd(PPh3)4 (3.0 mg, 0.003 mmol), and potassium carbonate (36 mg, 0.26 mmol). To the flask was added a water/DMF/CH3CN mixture (1:1:4.5; 0.1:0.1:0.6 mL), and the reaction mixture was degassed under nitrogen and heated at 80° C. for 6 hours. The cooled reaction mixture was diluted with water and 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 13.9 mg of the desired product as a yellow solid. MS (ES+APCI) m/z=534 (M+H) detected.

Workup

  1. customA dried 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 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-f1548076644c4affaee40b994f60514b
Source dataset
uspto-grants-2015_11
Patent number
US09174981B2

Reaction notes

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