Dichloromethane → N-(5-(2-tert-Butoxyethylcarbamoyl)-2-fluorophenyl)-7-(6-(3-(dimethylamino)propoxy)pyridin-3-yl)imidazo[1,2-a]pyridine-3-carboxamide

HRID 335279Notes

Reaction equation

HRID 335279 reaction equation
Br[C:2]1[CH:7]=[CH:6][N:5]2[C:8]([C:11]([NH:13][C:14]3[CH:19]=[C:18]([C:20](=[O:29])[NH:21][CH2:22][CH2:23][O:24][C:25]([CH3:28])([CH3:27])[CH3:26])[CH:17]=[CH:16][C:15]=3[F:30])=[O:12])=[CH:9][N:10]=[C:4]2[CH:3]=1.[CH3:31][N:32]([CH3:52])[CH2:33][CH2:34][CH2:35][O:36][C:37]1[CH:42]=[CH:41][C:40](B2OC(C)(C)C(C)(C)O2)=[CH:39][N:38]=1.C(=O)([O-])[O-].[Cs+].[Cs+].C(Cl)Cl>COCCOC.O>[C:25]([O:24][CH2:23][CH2:22][NH:21][C:20]([C:18]1[CH:17]=[CH:16][C:15]([F:30])=[C:14]([NH:13][C:11]([C:8]2[N:5]3[CH:6]=[CH:7][C:2]([C:40]4[CH:39]=[N:38][C:37]([O:36][CH2:35][CH2:34][CH2:33][N:32]([CH3:31])[CH3:52])=[CH:42][CH:41]=4)=[CH:3][C:4]3=[N:10][CH:9]=2)=[O:12])[CH:19]=1)=[O:29])([CH3:28])([CH3:27])[CH3:26]

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 10796Cesium carbonateHCID 17998906N,N-Dimethyl-3-((5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl)oxy)propan-1-amineHCID 712834867-Bromo-N-(5-(2-tert-butoxyethylcarbamoyl)-2-fluorophenyl)imidazo[1,2-a]pyridine-3-carboxamide2×

Product 1

HCID 71283417N-(5-(2-tert-Butoxyethylcarbamoyl)-2-fluorophenyl)-7-(6-(3-(dimethylamino)propoxy)pyridin-3-yl)imidazo[1,2-a]pyridine-3-carboxamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

7-Bromo-N-(5-(2-tert-butoxyethylcarbamoyl)-2-fluorophenyl)imidazo[1,2-a]pyridine-3-carboxamide (Intermediate 2A) (300 mg, 0.629 mmol), N,N-dimethyl-3-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yloxy)propan-1-amine (202 mg, 0.660 mmol) and cesium carbonate (819 mg, 2.51 mmol) were combined in 1,2-dimethoxyethane (7 ml) and water (3 ml). The mixture was degassed thoroughly refilling with nitrogen and treated with PdCl2(dppf).CH2Cl2 adduct (25.7 mg, 0.031 mmol). The mixture was once again degassed thoroughly refilling with nitrogen and heated using microwave radiation at 100° C. for 1 hr. The aqueous was removed by pipette and the organic portion was absorbed onto silica and purified by chromatography eluting with 0-20% MeOH in DCM. The resulting solid was recrystallised from EtOAc to afford the title compound;

Workup

  1. customThe mixture was degassed thoroughly
  2. additiontreated with PdCl2(dppf)
  3. customThe mixture was once again degassed thoroughly
  4. temperatureheated
  5. customat 100° C.
  6. customfor 1 hr
  7. customThe aqueous was removed by pipette
  8. customthe organic portion was absorbed onto silica
  9. custompurified by chromatography
  10. washeluting with 0-20% MeOH in DCM
  11. customThe resulting solid was recrystallised from EtOAc

Sources & evidence

ORD record
ord-5b735ec1c6e14c17be6ec6cfab07ecd0
Source dataset
uspto-grants-2014_11
Patent number
US08883819B2

Reaction notes

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