Dimethylformamide → 1-(4-Fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxylic acid [4-(6-nitrofuro[3,2-c]pyridin-7-yloxymethyl)phenyl]amide

HRID 912053Notes

Reaction equation

HRID 912053 reaction equation
CN(C=O)C.[H-].[Na+].[N+:8]([C:11]1[N:16]=[CH:15][C:14]2[CH:17]=[CH:18][O:19][C:13]=2[C:12]=1[OH:20])([O-:10])=[O:9].Br[CH2:22][C:23]1[CH:28]=[CH:27][C:26]([NH:29][C:30]([C:32]2[C:33](=[O:45])[N:34]([C:38]3[CH:43]=[CH:42][C:41]([F:44])=[CH:40][CH:39]=3)[CH:35]=[CH:36][CH:37]=2)=[O:31])=[CH:25][CH:24]=1>O>[N+:8]([C:11]1[N:16]=[CH:15][C:14]2[CH:17]=[CH:18][O:19][C:13]=2[C:12]=1[O:20][CH2:22][C:23]1[CH:28]=[CH:27][C:26]([NH:29][C:30]([C:32]2[C:33](=[O:45])[N:34]([C:38]3[CH:39]=[CH:40][C:41]([F:44])=[CH:42][CH:43]=3)[CH:35]=[CH:36][CH:37]=2)=[O:31])=[CH:25][CH:24]=1)([O-:10])=[O:9]

Participants

6

Reactant 4

HCID 6228Dimethylformamide3×HCID 24758Sodium hydrideHCID 578124576-Nitrofuro[3,2-c]pyridin-7-ol2×HCID 578126261-(4-Fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxylic acid (4-bromomethylphenyl)-amide

Product 1

HCID 578125811-(4-Fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxylic acid [4-(6-nitrofuro[3,2-c]pyridin-7-yloxymethyl)phenyl]amide

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
0 °C

Procedure

Into a DMF (1.5 ml) suspension of NaH (11.0 mg, 60% suspension in oil, 0.275 mmol), which was cooled at 0° C. under an atmosphere of nitrogen, was added the DMF (1.5 ml) solution of 6-nitrofuro[3,2-c]pyridin-7-ol (Intermediate 7) (45.1 mg, 0.248 mmol) dropwise. The mixture was stirred at 0° C. for 5 min and was then raised to rt and stirred at rt for 30 min. Then this reaction mixture was added dropwise into the DMF (4 ml) suspension of 1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxylic acid (4-bromomethylphenyl)-amide (0.248 mmol) at rt under an atmosphere of nitrogen. The combined mixture was stirred at rt for 1 h. After that time, the reaction mixture was poured into water. The solid was filtered off and washed with water to give a beige solid. It was triturated with EtOAc (4 ml). The solid was filtered off and the mother liquor was purified by TLC eluting with 2.5% MeOH/DCM 2 times to give the title compound as a yellow solid. 1H NMR (400 MHz, CDCl3): δ=5.58 (s, 2H), 6.59 (dd, J=6.8 & 7.2 Hz, 1H), 6.96 (d, J=2.4 Hz, 1H), 7.23-7.29 (m, 2H), 7.38-7.45 (m, 4H), 7.60 (dd, J=2.0 & 4.8 Hz, 1H), 7.73 (dd, J=2.4 & 6.8 Hz, 2H), 7.88 (d, J=2.0, 1H), 8.44 (s, 1H), 8.73 (dd, J=2.4 & 6.8 Hz, 1H), 11.84 (brs, 1H). MS (ES+): m/z 500.99 [MH+]. HPLC: tR=3.58 min (polar—5 min, ZQ3).

Workup

  1. temperaturewas then raised to rt
  2. stirringstirred at rt for 30 min
  3. stirringThe combined mixture was stirred at rt for 1 h
  4. filtrationThe solid was filtered off
  5. washwashed with water
  6. customto give a beige solid
  7. customIt was triturated with EtOAc (4 ml)
  8. filtrationThe solid was filtered off
  9. customthe mother liquor was purified by TLC
  10. washeluting with 2.5% MeOH/DCM 2 times

Sources & evidence

ORD record
ord-1e4254ee0f3649a1a84826e296dd3844
Source dataset
uspto-grants-2011_09
Patent number
US08022206B2

Reaction notes

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