2-Aminoquinoline → 2-(2,6-dichlorophenyl)-6,7-difluoro-3H-benzoimidazole-5-carboxylic acid quinolin-2-ylamide

HRID 1514911Notes

Reaction equation

HRID 1514911 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[C:9]1[NH:10][C:11]2[CH:17]=[C:16]([C:18](Cl)=[O:19])[C:15]([F:21])=[C:14]([F:22])[C:12]=2[N:13]=1.[N:23]1[C:32]2[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=2)[CH:26]=[CH:25][C:24]=1[NH2:33].CCN(C(C)C)C(C)C>C1COCC1>[N:23]1[C:32]2[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=2)[CH:26]=[CH:25][C:24]=1[NH:33][C:18]([C:16]1[C:15]([F:21])=[C:14]([F:22])[C:12]2[N:13]=[C:9]([C:3]3[C:2]([Cl:1])=[CH:7][CH:6]=[CH:5][C:4]=3[Cl:8])[NH:10][C:11]=2[CH:17]=1)=[O:19]

Participants

5

Reactant 3

HCID 113792-AminoquinolineHCID 81531DiisopropylethylamineHCID 866512642-(2,6-dichlorophenyl)-6,7-difluoro-3H-benzoimidazole-5-carbonyl chloride

Product 1

HCID 669652202-(2,6-dichlorophenyl)-6,7-difluoro-3H-benzoimidazole-5-carboxylic acid quinolin-2-ylamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

To a stirred suspension of 2-(2,6-dichlorophenyl)-6,7-difluoro-3H-benzoimidazole-5-carbonyl chloride (150 mg, 0.38 mmol) and quinolin-2-ylamine (55 mg, 0.38 mmol) in THF (10 mL) was added DIPEA (0.2 ml, 1.14 mmol) and the solution was heated at 60° C. for 4 days. The reaction was quenched with water and aqueous layer was extracted with EtOAc. The organic layer was washed with water, brine, dried with MgSO4, and filtered. The solvent was removed under reduced pressure and the residue was purified by flash chromatography using a gradient of heptane/EtOAc (4:1 to 100% EtOAc) to give 2-(2,6-dichlorophenyl)-6,7-difluoro-3H-benzoimidazole-5-carboxylic acid quinolin-2-ylamide as a white solid. 1H NMR (DMSO-d6, 400 MHz): δ 13.67 (s, 1H), 11.26 (s, 1H), 8.47 (d, 1H), 8.41 (d, 1H), 7.98 (d, 1H), 7.87 (d, 1H), 7.81 (d, 1H), 7.77 (m, 4H), 7.56 (m, 1H). MS (m/z) 469.1 (M+1); Retention time: 1.51 min (Method 10).

Workup

  1. customThe reaction was quenched with water and aqueous layer
  2. extractionwas extracted with EtOAc
  3. washThe organic layer was washed with water, brine
  4. dry with materialdried with MgSO4
  5. filtrationfiltered
  6. customThe solvent was removed under reduced pressure
  7. customthe residue was purified by flash chromatography

Sources & evidence

ORD record
ord-513d97a00f5c474da0ed683d757e2c3e
Source dataset
uspto-grants-2012_07
Patent number
US08222248B2

Reaction notes

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