4-Fluoroaniline → HCID 178432349, compound

HRID 1898442Notes

Reaction equation

HRID 1898442 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[NH:9][C:10]1[NH:22][C:21]2[C:16]3[N:17]=[C:18]([CH3:20])[O:19][C:15]=3[C:14]([C:23](O)=[O:24])=[CH:13][C:12]=2[N:11]=1.[F:26][C:27]1[CH:33]=[CH:32][C:30]([NH2:31])=[CH:29][CH:28]=1.[H-].[Na+]>C1C=CC=CC=1.S(Cl)(Cl)=O.C1COCC1>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[NH:9][C:10]1[NH:22][C:21]2[C:16]3[N:17]=[C:18]([CH3:20])[O:19][C:15]=3[C:14]([C:23]([NH:31][C:30]3[CH:32]=[CH:33][C:27]([F:26])=[CH:28][CH:29]=3)=[O:24])=[CH:13][C:12]=2[N:11]=1

Participants

7

Reactant 3

HCID 97314-FluoroanilineHCID 24758Sodium hydrideHCID 178432356HCID 178432356, compound

Product 1

HCID 178432349HCID 178432349, compoundYield 15.4%

Reagents, catalysts & solvents 3

HCID 241BenzeneSolventHCID 8028TetrahydrofuranSolventHCID 24386Thionyl ChlorideSolvent

Procedure

To a solution of 7-[(2,6-dichlorophenyl)amino]-2-methyl-8H-imidazo[4,5-e][1,3]benzoxazole-4-carboxylic acid (Intermediate-55, 0.100 g, 0.276 mmol) in benzene (4 mL), thionyl chloride (5.0 mL) was added at 5-10° C. The reaction mass was refluxed for 3 h. Thionyl chloride was removed under vacuum and stripped out with benzene. The solution of 4-fluoroaniline (0.091 g, 0.828 mmol) in THF (5.0 mL) was added 60% NaH (0.033 g, 0.825 mmol) under N2-atmosphere at 0-5° C. The solution was stirred for 30 minutes at same temperature and above prepared solution was added to reaction mixture. The reaction mass was stirred at RT for 1 h. The reaction mass was quenched in ice water and extracted with ethyl acetate. The obtained product was further purified by column chromatography on neutral alumina eluting with 1.5-2.0% MeOH:DCM to afford 0.020 g of the desired product. 1HNMR (DMSO-d6): δ 2.65 (s, 3H), 7.17-7.20 (m, 4H), 7.38-7.50 (m, 1H), 7.61 (s, 2H), 7.79 (s, 1H), 8.96-9.04 (m, 1H), 9.40-9.60 (s, 1H), 11-12 (s, 1H); MS [M+H]+: 470.23.

Workup

  1. temperatureThe reaction mass was refluxed for 3 h
  2. customThionyl chloride was removed under vacuum
  3. customabove prepared solution
  4. additionwas added to reaction mixture
  5. stirringThe reaction mass was stirred at RT for 1 h
  6. customThe reaction mass was quenched in ice water
  7. extractionextracted with ethyl acetate
  8. customThe obtained product was further purified by column chromatography on neutral alumina eluting with 1.5-2.0% MeOH

Sources & evidence

ORD record
ord-db053fffe0824613a8abeb7284d81dab
Source dataset
uspto-grants-2013_08
Patent number
US08519149B2

Reaction notes

Loading…