2-Fluorobenzoyl chloride → HCID 58486919, compound

HRID 874649Notes

Reaction equation

HRID 874649 reaction equation
[Cl: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:8]2[CH2:7][CH2:6][O:5][C:4]=2[CH:3]=1.[F:18][C:19]1[CH:27]=[CH:26][CH:25]=[CH:24][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>[Cl:1][C:2]1[C:10]([C:11]2[CH:12]=[CH:13][C:14]([NH:17][C:21]([C:20]3[CH:24]=[CH:25][CH:26]=[CH:27][C:19]=3[F:18])=[O:22])=[N:15][CH:16]=2)=[CH:9][C:8]2[CH2:7][CH2:6][O:5][C:4]=2[CH:3]=1

Participants

6

Reactant 4

HCID 98082-Fluorobenzoyl chlorideHCID 81531DiisopropylethylamineHCID 23716255Sodium bicarbonate methylene chlorideHCID 584867025-(6-Chloro-2,3-dihydro-5-benzofuranyl)-2-pyridinamine

Product 1

HCID 58486919HCID 58486919, compoundYield 45.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 5-(6-chloro-2,3-dihydrobenzo[3,4-b]furan-5-yl)-2-pyridylamine (144) (19 mg, 0.045 mmol) in 1 ml DCM was added 2-fluorobenzoyl chloride (16 μl, 3 eq) followed by addition of DIEA (39 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. Prep HPLC purification furnished N-[5-(6-chloro(2,3-dihydrobenzo[3,4-b]furan-5-yl))(2-pyridyl)](2-fluorophenyl)carboxamide (146) (7.6 mg, yield: 45.8%, purity>95%) 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
  5. customPrep HPLC purification

Sources & evidence

ORD record
ord-df19193bad254176a93c5b66869bb7ad
Source dataset
uspto-grants-2015_03
Patent number
US08980629B2

Reaction notes

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