Diisopropylethylamine → (2,6-difluorophenyl)-N-[5-(5-bromo(2,3-dihydrobenzo[3,4-b]furan-6-yl))(2-pyridyl)]carboxamide

HRID 1036118Notes

Reaction equation

HRID 1036118 reaction equation
[Br:1][C:2]1[C:10]([C:11]2[CH:12]=[CH:13][C:14]([NH2:17])=[N:15][CH:16]=2)=[CH:9][C:5]2[O:6][CH2:7][CH2:8][C:4]=2[CH:3]=1.[F:18][C:19]1[CH:27]=[CH:26][CH:25]=[C:24]([F:28])[C:20]=1[C:21](Cl)=[O:22].CCN(C(C)C)C(C)C.C([O-])(O)=O.[Na+].C(Cl)Cl>C(Cl)Cl>[F:18][C:19]1[CH:27]=[CH:26][CH:25]=[C:24]([F:28])[C:20]=1[C:21]([NH:17][C:14]1[CH:13]=[CH:12][C:11]([C:10]2[C:2]([Br:1])=[CH:3][C:4]3[CH2:8][CH2:7][O:6][C:5]=3[CH:9]=2)=[CH:16][N:15]=1)=[O:22]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 874382,6-Difluorobenzoyl chlorideHCID 23716255Sodium bicarbonate methylene chlorideHCID 584869705-(5-Bromo-2,3-dihydrobenzo[3,4-b]furan-6-yl)-2-pyridylamine

Product 1

HCID 58487299(2,6-difluorophenyl)-N-[5-(5-bromo(2,3-dihydrobenzo[3,4-b]furan-6-yl))(2-pyridyl)]carboxamideYield 81.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 5-(5-bromo-2,3-dihydrobenzo[3,4-b]furan-6-yl)-2-pyridylamine (139) (13 mg, 0.044 mmol) in 1 ml DCM was added 2,6-difluorobenzoyl chloride (11 μl, 0.088 mmol) followed by addition of DIEA (38 μl). The resulting solution was stirred at r.t. for overnight. The reaction mixture was worked up with aq. NaHCO3/DCM. DCM phase was washed with brine, concentrated to dryness. The residue was dissolved in 1 ml THF/MeOH/H2O (5:4:1) and stirred with 1N NaOH (100 μl) at r.t. for 2 h and before worked up with EA/aq. NaHCO3. Silica gel flash chromatography furnished (2,6-difluorophenyl)-N-[5-(5-bromo(2,3-dihydrobenzo[3,4-b]furan-6-yl))(2-pyridyl)]carboxamide (140) (15.5 mg, yield: 81.6%, purity>90%) as white solid.

Workup

  1. washDCM phase was washed with brine
  2. concentrationconcentrated to dryness
  3. dissolutionThe residue was dissolved in 1 ml THF/MeOH/H2O (5:4:1)
  4. stirringstirred with 1N NaOH (100 μl) at r.t. for 2 h

Sources & evidence

ORD record
ord-df25428469ff44ad8e2551c1c7fe8b46
Source dataset
uspto-grants-2013_10
Patent number
US08546403B2

Reaction notes

Loading…