Hydrochloric Acid → 4-bromo-2-cyclopropyl-1-(2-methyl-3-(trifluoromethyl)benzyl)-1H-benzo[d]imidazol-6-amine

HRID 1622496Notes

Reaction equation

HRID 1622496 reaction equation
[Br:1][C:2]1[C:10]2[N:9]=[C:8]([CH:11]3[CH2:13][CH2:12]3)[N:7]([CH2:14][C:15]3[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([F:24])([F:23])[F:22])[C:16]=3[CH3:25])[C:6]=2[CH:5]=[C:4]([N+:26]([O-])=O)[CH:3]=1.O.O.[Sn](Cl)Cl.Cl.C(=O)([O-])[O-].[Na+].[Na+]>CO>[Br:1][C:2]1[C:10]2[N:9]=[C:8]([CH:11]3[CH2:12][CH2:13]3)[N:7]([CH2:14][C:15]3[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([F:23])([F:22])[F:24])[C:16]=3[CH3:25])[C:6]=2[CH:5]=[C:4]([NH2:26])[CH:3]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 10340Sodium CarbonateHCID 61436Stannous chloride dihydrateHCID 866878514-bromo-2-cyclopropyl-1-(2-methyl-3-(trifluoromethyl)benzyl)-6-nitro-1H-benzo[d]imidazole

Product 1

HCID 866878524-bromo-2-cyclopropyl-1-(2-methyl-3-(trifluoromethyl)benzyl)-1H-benzo[d]imidazol-6-amineYield 62.4%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

To a 250 mL round-bottom flask containing MeOH (70 mL) was added crude 4-bromo-2-cyclopropyl-1-(2-methyl-3-(trifluoromethyl)benzyl)-6-nitro-1H-benzo[d]imidazole (5.87 g, 12.92 mmol), tin(II) chloride dihydrate (8.75 g, 38.8 mmol) and hydrochloric acid (5.38 mL, 64.6 mmol). The resultant suspension was heated to 50° C. and monitored by LC/MS. By LC/MS analysis the reaction was complete in 30 minutes. After the reaction had cooled to rt, the majority of the MeOH was removed in-vacuo and sodium carbonate (64.6 mL, 64.6 mmol) was added slowly to adjust the pH to about 10 and the mixture was extracted with Et2O (3×100 mL) and the organic was washed with H2O and brine and dried over MgSO4 and filtered. The solvent was removed in-vacuo leaving the desired compound (3.42 g, 8.06 mmol, 62.4% yield) as crude brown solid that by LC/MS was sufficiently pure to use in the next step. NMR was consistent with desired product. MS (ES+) m/e: 423.1, 423.8 [M+H]+; 1H NMR (400 MHz, METHANOL-d4) δ ppm 7.57 (d, J=7.83 Hz, 1H), 7.19 (t, J=7.83 Hz, 1H), 6.84-6.95 (m, 1H), 6.35-6.58 (m, 2H), 5.51 (s, 1H), 5.42 (s, 1H), 2.57 (s, 3H), 1.84-1.98 (m, 1H), 1.05-1.17 (m, 2H), 0.87-1.05 (m, 2H)

Workup

  1. additionwas added slowly
  2. extractionthe mixture was extracted with Et2O (3×100 mL)
  3. washthe organic was washed with H2O and brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. customThe solvent was removed in-vacuo

Sources & evidence

ORD record
ord-2ea5fe199335462094f2c5d779322094
Source dataset
uspto-grants-2014_07
Patent number
US08778937B2

Reaction notes

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