Trifluoroacetic anhydride → N-(7-(2-chlorophenyl)-5-oxo-5,6-dihydro-2,6-naphthyridin-3-yl)cyclopropanecarboxamide

HRID 468857Notes

Reaction equation

HRID 468857 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[N+:9]([O-])=[CH:10][C:11]2[C:16]([CH:17]=1)=[CH:15][N:14]=[C:13]([NH:18][C:19]([CH:21]1[CH2:23][CH2:22]1)=[O:20])[CH:12]=2.FC(F)(F)C(OC(=O)C(F)(F)F)=[O:28]>O1CCCC1.C(OCC)(=O)C>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[NH:9][C:10](=[O:28])[C:11]2[CH:12]=[C:13]([NH:18][C:19]([CH:21]3[CH2:23][CH2:22]3)=[O:20])[N:14]=[CH:15][C:16]=2[CH:17]=1

Participants

5

Reactant 2

HCID 9845Trifluoroacetic anhydrideHCID 679746713-(2-Chlorophenyl)-7-(cyclopropanecarboxamido)-2,6-naphthyridine 2-oxide

Product 1

HCID 68095319N-(7-(2-chlorophenyl)-5-oxo-5,6-dihydro-2,6-naphthyridin-3-yl)cyclopropanecarboxamideYield 29.4%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a slurry of 3-(2-chlorophenyl)-7-(cyclopropanecarboxamido)-2,6-naphthyridine 2-oxide (50 mg, 0.1 mmol) in tetrahydrofuran (0.5 mL) at 0° C. was added trifluoroacetic anhydride (0.04 mL, 0.29 mmol) dropwise over 2 minutes. The mixture was allowed to warm to room temperature and stir for 2 hours. The reaction mixture was diluted with ethyl acetate (50 mL) and washed with saturated sodium bicarbonate solution (10 mL). The organic layer was separated, dried over sodium sulfate, filtered, and evaporated in vacuo to afford a residue that was purified by reverse phase HPLC (5-85% acetonitrile in water with 0.1% formic acid over 14 min) to afford the title compound as a yellow solid (10 mg, 20%). 1H NMR (400 MHz, DMSO) δ 11.10 (s, 1H), 10.33 (s, 1H), 9.51 (s, 1H), 8.86 (s, 1H), 8.54 (s, 1H), 7.62-7.52 (m, 1H), 7.53-7.38 (m, 3H), 2.08 (m, 1H), 0.88 (m, 4H). LCMS (Method E): RT=3.759 min, M+H+=340.0.

Workup

  1. washwashed with saturated sodium bicarbonate solution (10 mL)
  2. customThe organic layer was separated
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. customevaporated in vacuo
  6. customto afford a residue that
  7. customwas purified by reverse phase HPLC (5-85% acetonitrile in water with 0.1% formic acid over 14 min)

Sources & evidence

ORD record
ord-45136cdb09c24c10b642b10ecaef33b6
Source dataset
uspto-grants-2014_01
Patent number
US08623889B2

Reaction notes

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