5-Bromo-2-furanecarboxylic acid → HCID 51158946, compound

HRID 1056614Notes

Reaction equation

HRID 1056614 reaction equation
[Br:1][C:2]1[O:6][C:5]([C:7]([OH:9])=O)=[CH:4][CH:3]=1.[F:10][C:11]1[CH:17]=[CH:16][CH:15]=[C:14]([F:18])[C:12]=1[NH2:13].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.C(OCC)(=O)C.O>[Br:1][C:2]1[O:6][C:5]([C:7]([NH:13][C:12]2[C:11]([F:10])=[CH:17][CH:16]=[CH:15][C:14]=2[F:18])=[O:9])=[CH:4][CH:3]=1

Participants

8

Reactant 4

HCID 685115-Bromo-2-furanecarboxylic acidHCID 796472,6-DifluoroanilineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)

Product 1

HCID 51158946HCID 51158946, compoundYield 13%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 5-bromofuran-2-carboxylic acid acid (2.0 g, 10.4 mmol) in DMF (30 mL), 2,6-difluoroaniline (1.27 mL, 12.5 mmol), DIPEA (3.66 mL, 20.9 mmol) and HATU (4.78 g, 12.5 mmol) were successively added. The resulting mixture was stirred at RT for 3 h. The reaction mixture was diluted with ethyl acetate (50 mL) followed by water (30 mL). The layers were separated and the aqueous layer was extracted with ethyl acetate (3×20 mL). The combined organic layers were washed with brine (50 mL), dried (Na2SO4) and filtered. The filtrate was concentrated under vacuum. The crude product was purified by flash column chromatography (silica gel, 20% ethyl acetate in hexane) to afford 400 mg (13%) of the title compound as white solid. 1HNMR (400 MHz, CDCl3) δ 7.57 (s, D2O exchangeable, 1H), 7.31-7.25 (m, 1H), 7.24 (d, J=3.5 Hz, 1H), 7.01 (t, J=7.5 Hz, 2H), 6.54 (d, J=3.5 Hz, 1H); ESI-MS (m/z) 302, 304 [(MH)+ Br79,81].

Workup

  1. customThe layers were separated
  2. extractionthe aqueous layer was extracted with ethyl acetate (3×20 mL)
  3. washThe combined organic layers were washed with brine (50 mL)
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated under vacuum
  7. customThe crude product was purified by flash column chromatography (silica gel, 20% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-85ab7749b29d47319cbad6b56ba57cdb
Source dataset
uspto-grants-2016_07
Patent number
US09399638B2

Reaction notes

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