Water → HCID 178425051, compound

HRID 1898377Notes

Reaction equation

HRID 1898377 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH3:8])[C:3]=1[NH:9][C:10]1[NH:11][C:12]2[C:18]3[CH2:19][C:20]([CH3:23])([CH3:22])[O:21][C:17]=3[C:16]([C:24](O)=[O:25])=[CH:15][C:13]=2[N:14]=1.[F:27][C:28]([F:37])([F:36])[C:29]1[CH:34]=[CH:33][C:32]([NH2:35])=[CH:31][CH:30]=1.CCN(C(C)C)C(C)C.O>C1C=CC=CC=1.S(Cl)(Cl)=O.C1COCC1>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH3:8])[C:3]=1[NH:9][C:10]1[NH:11][C:12]2[C:18]3[CH2:19][C:20]([CH3:23])([CH3:22])[O:21][C:17]=3[C:16]([C:24]([NH:35][C:32]3[CH:33]=[CH:34][C:29]([C:28]([F:27])([F:36])[F:37])=[CH:30][CH:31]=3)=[O:25])=[CH:15][C:13]=2[N:14]=1

Participants

8

Reactant 4

HCID 962WaterHCID 99644-(Trifluoromethyl)anilineHCID 81531DiisopropylethylamineHCID 178425067HCID 178425067, compound

Product 1

HCID 178425051HCID 178425051, compoundYield 8.7%

Reagents, catalysts & solvents 3

HCID 241BenzeneSolventHCID 8028TetrahydrofuranSolvent2×HCID 24386Thionyl ChlorideSolvent2×

Procedure

To a solution of 2-[(2-chloro-6-methylphenyl)amino]-7,7-dimethyl-7,8-dihydro-1H-furo[3,2-e]benzimidazole-5-carboxylic acid (Intermediate-35, 0.100 g, 0.268 mmol) in benzene (2 mL), thionyl chloride (3.0 mL) was added at 5-10° C. and the reaction mass was refluxed for 3 h. To the reaction mixture, stirred solution of 4-trifluoromethyl phenyl amine (0.065 g, 0.403 mmol) and DIPEA (0.069 g, 0.534 mmol) in THF (10.0 mL) for 1 h at RT under N2-atmosphere was added and stirring was continued for another 1 h at RT. Excess of thionyl chloride was co-evaporated with THF under vacuum. Water was added to the reaction mass and it was extracted with ethyl acetate. The organic layer was separated, dried over anhydrous sodium sulphate and concentrated. The obtained crude product was purified by column chromatography on neutral alumina eluting with 0.7-1.0% MeOH:DCM to afford 0.012 g of the desired product. 1HNMR (DMSO-d6): δ 1.58 (s, 6H), 2.24 (s, 3H), 3.44 (s, 2H), 7.25-7.31 (m, 2H), 7.42 (d, J=7.2 Hz, 1H), 7.50 (s, 1H), 7.70 (d, J=8.7 Hz, 2H), 7.91 (d, J=8.4 Hz, 2H), 9.09 (s, 1H), 10.01 (s, 1H), 10.94 (s, 1H); MS [M−H]−: 513.42.

Workup

  1. temperaturethe reaction mass was refluxed for 3 h
  2. additionwas added
  3. extractionwas extracted with ethyl acetate
  4. customThe organic layer was separated
  5. dry with materialdried over anhydrous sodium sulphate
  6. concentrationconcentrated
  7. customThe obtained crude product
  8. customwas purified by column chromatography on neutral alumina eluting with 0.7-1.0% MeOH

Sources & evidence

ORD record
ord-c74b73b08b7a4b41ade320601ecf11c5
Source dataset
uspto-grants-2013_08
Patent number
US08519149B2

Reaction notes

Loading…