Tri-tert-butylphosphine tetrafluoroborate → Ethyl 3-(3-(5-(3,4-difluorobenzylcarbamoyl)-2-fluorophenylcarbamoyl)imidazo[1,2-a]pyridin-7-yl)propanoate

HRID 335286Notes

Reaction equation

HRID 335286 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:31])[NH:21][CH2:22][C:23]4[CH:28]=[CH:27][C:26]([F:29])=[C:25]([F:30])[CH:24]=4)[CH:17]=[CH:16][C:15]=3[F:32])=[O:12])=[CH:9][N:10]=[C:4]2[CH:3]=1.F[B-](F)(F)F.C([PH+](C(C)(C)C)C(C)(C)C)(C)(C)C.[Br-].[CH2:52]([O:54][C:55](=[O:59])[CH2:56][CH2:57][Zn+])[CH3:53]>C1COCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[F:30][C:25]1[CH:24]=[C:23]([CH:28]=[CH:27][C:26]=1[F:29])[CH2:22][NH:21][C:20]([C:18]1[CH:17]=[CH:16][C:15]([F:32])=[C:14]([NH:13][C:11]([C:8]2[N:5]3[CH:6]=[CH:7][C:2]([CH2:57][CH2:56][C:55]([O:54][CH2:52][CH3:53])=[O:59])=[CH:3][C:4]3=[N:10][CH:9]=2)=[O:12])[CH:19]=1)=[O:31]

Participants

6

Reactant 3

HCID 2734635Tri-tert-butylphosphine tetrafluoroborateHCID 712831817-bromo-N-(5-(3,4-difluorobenzylcarbamoyl)-2-fluorophenyl)imidazo[1,2-a]pyridine-3-carboxamide2×HCID 178471816HCID 178471816, compound

Product 1

HCID 71283043Ethyl 3-(3-(5-(3,4-difluorobenzylcarbamoyl)-2-fluorophenylcarbamoyl)imidazo[1,2-a]pyridin-7-yl)propanoate

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

7-Bromo-N-(5-(3,4-difluorobenzylcarbamoyl)-2-fluorophenyl)imidazo[1,2-a]pyridine-3-carboxamide (Intermediate 3A) (1 g, 1.987 mmol), Pd2(dba)3 (0.091 g, 0.099 mmol) and tritertbutylphosphonium tetrafluoroborate (0.058 g, 0.199 mmol) were combined in THF (60 ml) under nitrogen and the mixture was degassed thoroughly refilling with nitrogen (×3). (3-Ethoxy-3-oxopropyl)zinc(II) bromide (19.87 ml, 9.93 mmol) was added and the mixture was heated at 60° C. for 100 mins. After cooling to RT, the mixture was absorbed onto silica and purification by chromatography eluting with 0-6% MeOH in DCM afforded a yellow oil which was triturated with EtOAc to give the title compound;

Workup

  1. customthe mixture was degassed thoroughly
  2. temperatureAfter cooling to RT
  3. customthe mixture was absorbed onto silica and purification by chromatography
  4. washeluting with 0-6% MeOH in DCM
  5. customafforded a yellow oil which
  6. customwas triturated with EtOAc

Sources & evidence

ORD record
ord-06170f940b2a49999fb86f4774cf1d7d
Source dataset
uspto-grants-2014_11
Patent number
US08883819B2

Reaction notes

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