Sodium hydride → HCID 178482428, compound

HRID 2203429Notes

Reaction equation

HRID 2203429 reaction equation
[NH2:1][C:2]1[NH:6][C:5]2[CH:7]=[CH:8][C:9]([C:11]3[CH:16]=[C:15]([Cl:17])[CH:14]=[CH:13][C:12]=3[OH:18])=[CH:10][C:4]=2[N:3]=1.[H-].[Na+].[F:21][C:22]1[CH:27]=[C:26](F)[C:25]([F:29])=[CH:24][C:23]=1[S:30]([N:33]([CH3:39])[C:34]1[S:38][N:37]=[CH:36][N:35]=1)(=[O:32])=[O:31]>CN(C)C=O.O>[NH2:1][C:2]1[NH:6][C:5]2[CH:7]=[CH:8][C:9]([C:11]3[CH:16]=[C:15]([Cl:17])[CH:14]=[CH:13][C:12]=3[O:18][C:26]3[C:25]([F:29])=[CH:24][C:23]([S:30]([N:33]([CH3:39])[C:34]4[S:38][N:37]=[CH:36][N:35]=4)(=[O:31])=[O:32])=[C:22]([F:21])[CH:27]=3)=[CH:10][C:4]=2[N:3]=1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 89545277HCID 89545277, compoundHCID 178508154HCID 178508154, compound

Product 1

HCID 178482428HCID 178482428, compoundYield 63%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 2-(2-amino-1H-benzo[d]imidazol-5-yl)-4-chlorophenol (0.40 g, 1.5 mmol) in N,N-dimethylformamide (5 mL) at 0° C. was added sodium hydride (60% w/w dispersion in mineral oil, 0.07 g, 1.8 mmol). The mixture was allowed to warm to ambient temperature and stirred for 1 h. 2,4,5-Trifluoro-N-methyl-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide (0.52 g, 1.7 mmol) was added and the mixture was stirred at ambient temperature for 16 h. The mixture was partitioned between ethyl acetate (200 mL) and water (20 mL). The organic phase was washed with water (10 mL) and brine (2×10 mL), dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was purified by column chromatography eluting with a 0-10% gradient of methanol in ethyl acetate, followed by trituration in hexanes. The solid thus obtained was suspended in water (5 mL) and lyophilized to afford 4-(2-(2-amino-1H-benzo[d]imidazol-5-yl)-4-chlorophenoxy)-2,5-difluoro-N-methyl-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide as a beige solid in 63% yield (0.344 g): 1H NMR (300 MHz, CDCl3) δ10.78 (br s, 1H), 8.42 (d, J=1.9 Hz, 1H), 7.94-7.86 (m, 1H), 7.52-7.48 (m, 1H), 7.45-7.37 (m, 1H), 7.29 (dd, J=8.7, 1.6 Hz, 1H), 7.13 (s, 1H), 7.10-6.99 (m, 2H), 6.91 (d, J=8.1 Hz, 1H), 6.25 (s, 2H), 3.31 (s, 3H); 19F NMR (282 MHz, DMSO-d6) δ −108.7 (d, J=15.0 Hz, 1F), −135.1 (d, J=15.1 Hz, 1F); MS (ES+) m/z 548.7 (M+1), 550.7 (M+1).

Workup

  1. stirringthe mixture was stirred at ambient temperature for 16 h
  2. customThe mixture was partitioned between ethyl acetate (200 mL) and water (20 mL)
  3. washThe organic phase was washed with water (10 mL) and brine (2×10 mL)
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by column chromatography
  7. washeluting with a 0-10% gradient of methanol in ethyl acetate
  8. customThe solid thus obtained

Sources & evidence

ORD record
ord-8d8e6ff22ccb4572a253ca115eda920d
Source dataset
uspto-grants-2016_06
Patent number
US09365578B2

Reaction notes

Loading…