Diisopropylethylamine → N-(1-(6-(2,2,2-trifluoroethoxy)pyridin-3-yl)ethyl)benzo[d]isoxazole-3-carboxamide

HRID 623576Notes

Reaction equation

HRID 623576 reaction equation
Cl.[F:2][C:3]([F:16])([F:15])[CH2:4][O:5][C:6]1[N:11]=[CH:10][C:9]([CH:12]([NH2:14])[CH3:13])=[CH:8][CH:7]=1.C(N(CC)C(C)C)(C)C.[O:26]1[C:30]2[CH:31]=[CH:32][CH:33]=[CH:34][C:29]=2[C:28]([C:35](Cl)=[O:36])=[N:27]1>ClCCl.C(OCC)(=O)C>[F:16][C:3]([F:2])([F:15])[CH2:4][O:5][C:6]1[N:11]=[CH:10][C:9]([CH:12]([NH:14][C:35]([C:28]2[C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=3[O:26][N:27]=2)=[O:36])[CH3:13])=[CH:8][CH:7]=1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 10419807Benzo[d]isoxazole-3-carbonyl ChlorideHCID 675094131-[6-(2,2,2-Trifluoroethoxy)-pyridin-3-yl]-ethylamine hydrochloride

Product 1

HCID 67511565N-(1-(6-(2,2,2-trifluoroethoxy)pyridin-3-yl)ethyl)benzo[d]isoxazole-3-carboxamideYield 32%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (−)-1-(6-(2,2,2-trifluoroethoxy)pyridin-3-yl)ethanamine hydrochloride (20 mg, 0.078 mmol, Amine-1, single enantiomer) and N,N-diisopropylethylamine (0.054 mL, 0.31 mmol) in dichloromethane (0.5 mL) is added dropwise a solution of benzo[d]isoxazole-3-carbonyl chloride (17 mg, 0.094 mmol) in dichloromethane (0.5 mL) at room temperature. The reaction mixture is stirred at room temperature for 1 hour. The mixture is diluted with ethyl acetate (3 mL) and washed with water (1.5 mL). The organic layer is dried over sodium sulfate, and concentrated under reduced pressure. The residue is purified by column chromatography on NH-silica gel eluting with ethyl acetate and then preparative LC-MS to give 9.1 mg (32% yield) of the title compound.

Workup

  1. washwashed with water (1.5 mL)
  2. dry with materialThe organic layer is dried over sodium sulfate
  3. concentrationconcentrated under reduced pressure
  4. customThe residue is purified by column chromatography on NH-silica gel eluting with ethyl acetate

Sources & evidence

ORD record
ord-b296a370e2024324b87d64f57abd9c76
Source dataset
uspto-grants-2016_04
Patent number
US09302991B2

Reaction notes

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