Diisopropylethylamine → HCID 58487350, compound

HRID 2272233Notes

Reaction equation

HRID 2272233 reaction equation
[CH3:1][C:2]1([CH3:19])[CH2:6][O:5][C:4]2[CH:7]=[C:8]([CH3:18])[C:9]([C:11]3[N:12]=[CH:13][C:14]([NH2:17])=[N:15][CH:16]=3)=[CH:10][C:3]1=2.[F:20][C:21]1[CH:29]=[CH:28][CH:27]=[C:26]([F:30])[C:22]=1[C:23](Cl)=[O:24].CCN(C(C)C)C(C)C.C([O-])(O)=O.[Na+].C(Cl)Cl>C(Cl)Cl>[F:20][C:21]1[CH:29]=[CH:28][CH:27]=[C:26]([F:30])[C:22]=1[C:23]([NH:17][C:14]1[CH:13]=[N:12][C:11]([C:9]2[C:8]([CH3:18])=[CH:7][C:4]3[O:5][CH2:6][C:2]([CH3:19])([CH3:1])[C:3]=3[CH:10]=2)=[CH:16][N:15]=1)=[O:24]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 874382,6-Difluorobenzoyl chlorideHCID 23716255Sodium bicarbonate methylene chlorideHCID 58486872HCID 58486872, compound

Product 1

HCID 58487350HCID 58487350, compoundYield 35.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 5-(3,3,6-trimethyl-2,3-dihydrobenzo[3,4-b]furan-5-yl)pyrazine-2-ylamine (177) (19 mg, 0.075 mmol) in 1 ml DCM was added 2,6-difluorobenzoyl chloride (19 μl, 2 eq) followed by addition of DIEA (65 μl). The resulting solution was stirred at r.t. for 1 h. 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 (400 μl) at 60° C. for 1 h before worked up with EA/brine. Prep HPLC purification furnished (2,6-difluorophenyl)-N-[5-(3,3,6-trimethyl(2,3-dihydrobenzo[b]furan-5-yl))pyrazin-2-yl]carboxamide (178) (10.5 mg, yield: 35.4%, purity>95%) as off-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 (400 μl) at 60° C. for 1 h
  5. customPrep HPLC purification

Sources & evidence

ORD record
ord-44363f609a4d4ca39b1a8db593f7bc0c
Source dataset
uspto-grants-2015_09
Patent number
US09120751B2

Reaction notes

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