4-bromo-2-(difluoromethyl)-1-(2-methyl-3-(trifluoromethyl)benzyl)-6-nitro-1H-benzo[d]imidazole → 4-bromo-2-(difluoromethyl)-1-(2-methyl-3-(trifluoromethyl)benzyl)-1H-benzo[d]imidazol-6-amine

HRID 1622482Notes

Reaction equation

HRID 1622482 reaction equation
[Br:1][C:2]1[C:10]2[N:9]=[C:8]([CH:11]([F:13])[F:12])[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>C(O)(=O)C.[Zn]>[Br:1][C:2]1[C:10]2[N:9]=[C:8]([CH:11]([F:13])[F:12])[N:7]([CH2:14][C:15]3[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([F:24])([F:22])[F:23])[C:16]=3[CH3:25])[C:6]=2[CH:5]=[C:4]([NH2:26])[CH:3]=1

Participants

4

Reactant 1

HCID 866878404-bromo-2-(difluoromethyl)-1-(2-methyl-3-(trifluoromethyl)benzyl)-6-nitro-1H-benzo[d]imidazole

Product 1

HCID 866878414-bromo-2-(difluoromethyl)-1-(2-methyl-3-(trifluoromethyl)benzyl)-1H-benzo[d]imidazol-6-amine

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 176Acetic AcidSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of 4-bromo-2-(difluoromethyl)-1-(2-methyl-3-(trifluoromethyl)benzyl)-6-nitro-1H-benzo[d]imidazole (830 mg, 1.788 mmol) and zinc (701 mg, 10.73 mmol) in Acetic Acid (15 mL) was stirred and heated to 60° C. The reaction was monitored by LC/MS. After 90 minutes, a substantial amount of desired product was detected by LC/MS. The reaction was allowed to sit overnight and the next day the mixture was filtered through celite washing with HOAc. The filtrate was concentrated in-vacuo and the resulting residue, while appearing relatively clean and homogeneous by LC/MS, was a mixture of 2 compounds as indicated by TLC. The residue was loaded on a 10 g silica column and eluted with 12% EtOAc/hex for 6 column volumes then a gradient was run from 12% to 35% EtOAc/hex over 15 column volumes successfully separating the two closely eluting compounds. The early eluting compound was the desired product and the fractions were combined and concentrated to give 4-bromo-2-(difluoromethyl)-1-(2-methyl-3-(trifluoromethyl)benzyl)-1H-benzo[d]imidazol-6-amine (310 mg, 0.714 mmol, 39.9% yield) as a light yellow solid. LC/MS: MS (ES+) m/e 434.3 [M+H]+; 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 7.56 (d, J=7.83 Hz, 1H), 7.12 (t, J=7.83 Hz, 1H), 7.06 (s, 1H), 6.86-7.01 (m, 2H), 6.80 (s, 1H), 6.52 (d, J=7.83 Hz, 1H), 6.23 (d, J=2.02 Hz, 1H), 5.46 (s, 2H), 2.52 (s, 3H)

Sources & evidence

ORD record
ord-1e6e19d44e514c7b968a75cf63d79ba9
Source dataset
uspto-grants-2014_07
Patent number
US08778937B2

Reaction notes

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