Dichloromethane → 7-(1-Methyl-1H-pyrazol-5-yl)-N-(2-methyl-5-(2-(4-methylpiperazin-1-yl)benzylcarbamoyl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide

HRID 335270Notes

Reaction equation

HRID 335270 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:36])[NH:21][CH2:22][C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=4[N:29]4[CH2:34][CH2:33][N:32]([CH3:35])[CH2:31][CH2:30]4)[CH:17]=[CH:16][C:15]=3[CH3:37])=[O:12])=[CH:9][N:10]=[C:4]2[CH:3]=1.[CH3:38][N:39]1[C:43](B2OC(C)(C)C(C)(C)O2)=[CH:42][CH:41]=[N:40]1.C(=O)([O-])[O-].[Cs+].[Cs+].C(Cl)Cl>CN(C=O)C.N.CO.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].[Pd]>[CH3:38][N:39]1[C:43]([C:2]2[CH:7]=[CH:6][N:5]3[C:8]([C:11]([NH:13][C:14]4[CH:19]=[C:18]([C:20](=[O:36])[NH:21][CH2:22][C:23]5[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=5[N:29]5[CH2:34][CH2:33][N:32]([CH3:35])[CH2:31][CH2:30]5)[CH:17]=[CH:16][C:15]=4[CH3:37])=[O:12])=[CH:9][N:10]=[C:4]3[CH:3]=2)=[CH:42][CH:41]=[N:40]1

Participants

10

Reactant 4

HCID 6344DichloromethaneHCID 10796Cesium carbonateHCID 49129081-methyl-5-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 712831077-Bromo-N-(2-methyl-5-(2-(4-methylpiperazin-1-yl)benzylcarbamoyl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide

Product 1

HCID 712833787-(1-Methyl-1H-pyrazol-5-yl)-N-(2-methyl-5-(2-(4-methylpiperazin-1-yl)benzylcarbamoyl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide

Reagents, catalysts & solvents 5

HCID 23938PalladiumCatalystHCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 222AmmoniaSolventHCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Procedure

Under nitrogen, a mixture comprising 7-bromo-N-(2-methyl-5-(2-(4-methylpiperazin-1-yl)benzylcarbamoyl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide (step 1) (77.8 mg, 0.125 mmol), 1-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (51.9 mg, 0.249 mmol) and cesium carbonate (40.6 mg, 0.125 mmol) in DMF (1 ml) was treated with PdCl2(dppf).CH2Cl2 adduct (50.9 mg, 0.062 mmol) and heated at 110° C. for 1 hr. The solvent was removed in vacuo and purification by chromatography on silica eluting with 0-20% 2M NH3 in MeOH/DCM afforded a black solid. The solid was dissolved in 7M NH3 in MeOH (12 ml) and passed through a 1 g Pd scavenger cartridge. The solvent was removed in vacuo and the resulting solid was dried to yield the title compound;

Workup

  1. customThe solvent was removed in vacuo and purification by chromatography on silica eluting with 0-20% 2M NH3 in MeOH/DCM
  2. customafforded a black solid
  3. customThe solvent was removed in vacuo
  4. customthe resulting solid was dried

Sources & evidence

ORD record
ord-0b683eb449c64828bbebc6f7e84ff7bb
Source dataset
uspto-grants-2014_11
Patent number
US08883819B2

Reaction notes

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