Ammonium Hydroxide → 7-[(2,5-Dioxopyrrolidin-1-yl)methyl]-8-fluoro-4-(4-fluorophenyl)quinoline-2-carboxamide

HRID 922801Notes

Reaction equation

HRID 922801 reaction equation
[O:1]=[C:2]1[CH2:6][CH2:5][C:4](=[O:7])[N:3]1[CH2:8][C:9]1[C:18]([F:19])=[C:17]2[C:12]([C:13]([C:23]3[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=3)=[CH:14][C:15]([C:20](O)=[O:21])=[N:16]2)=[CH:11][CH:10]=1.C[N:31](C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[OH-].[NH4+]>CN(C=O)C>[O:1]=[C:2]1[CH2:6][CH2:5][C:4](=[O:7])[N:3]1[CH2:8][C:9]1[C:18]([F:19])=[C:17]2[C:12]([C:13]([C:23]3[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=3)=[CH:14][C:15]([C:20]([NH2:31])=[O:21])=[N:16]2)=[CH:11][CH:10]=1

Participants

5

Reactant 3

HCID 14923Ammonium HydroxideHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 895451337-[(2,5-Dioxopyrrolidin-1-yl)methyl]-8-fluoro-4-(4-fluorophenyl)quinoline-2-carboxylic acid

Product 1

HCID 895547857-[(2,5-Dioxopyrrolidin-1-yl)methyl]-8-fluoro-4-(4-fluorophenyl)quinoline-2-carboxamideYield 63.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

TEA (105 μl, 0.757 mmol) was added to a solution of 7-[(2,5-dioxopyrrolidin-1-yl)methyl]-8-fluoro-4-(4-fluorophenyl)quinoline-2-carboxylic acid 7-12 (100 mg, 0.252 mmol) and HATU (96 mg, 0.252 mmol) in DMF (1262 μl). Ammonium Hydroxide (50.5 μl, 0.757 mmol) was added and the reaction stirred for 15 min at rt. The reaction was quenched with aqueous sodium hydrogen carbonate (saturated) and the mixture was extracted with ethyl acetate (×3). The combined organic fractions were dried (MgSO4), filtered and the solvent was evaporated under reduced pressure. The residue was purified by column chromatography on a silica gel column, eluting with EtOAc/hexane (0-100%) to afford 7-[(2,5-dioxopyrrolidin-1-yl)methyl]-8-fluoro-4-(4-fluorophenyl)quinoline-2-carboxamide 7-13 (63 mg, 63% yield) as a white solid, LCMS shows the compound is 100% pure 1H NMR (500 MHz, CDCl3): δ 8.28 (1H, s), 8.14 (1H, s), 7.68 (1H, d, J=8.85 Hz), 7.54 (1H, dd, J=8.86, 6.65 Hz), 7.50-7.46 (2H, m), 7.25-7.20 (2H, m), 5.69 (1H, s), 4.99 (2H, s), 2.78 (4H, s). LRMS m/z (M+H)+ 396.2 found, 396.1 required.

Workup

  1. customThe reaction was quenched with aqueous sodium hydrogen carbonate (saturated)
  2. extractionthe mixture was extracted with ethyl acetate (×3)
  3. dry with materialThe combined organic fractions were dried (MgSO4)
  4. filtrationfiltered
  5. customthe solvent was evaporated under reduced pressure
  6. customThe residue was purified by column chromatography on a silica gel column
  7. washeluting with EtOAc/hexane (0-100%)

Sources & evidence

ORD record
ord-78863091809241c3880bc872a0006718
Source dataset
uspto-grants-2016_03
Patent number
US09278960B2

Reaction notes

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