Bis(2-bromoethyl) ether → 4-(7-bromo-2-methyl-3-(2-methyl-3-(trifluoromethyl)benzyl)-3H-benzo[d]imidazol-5-yl)morpholine

HRID 1622446Notes

Reaction equation

HRID 1622446 reaction equation
[Br:1][C:2]1[C:7]2[N:8]=[C:9]([CH3:23])[N:10]([CH2:11][C:12]3[CH:17]=[CH:16][CH:15]=[C:14]([C:18]([F:21])([F:20])[F:19])[C:13]=3[CH3:22])[C:6]=2[CH:5]=[C:4]([NH2:24])[CH:3]=1.Br[CH2:26][CH2:27][O:28][CH2:29][CH2:30]Br.CCN(C(C)C)C(C)C>C(O)CO.O>[Br:1][C:2]1[C:7]2[N:8]=[C:9]([CH3:23])[N:10]([CH2:11][C:12]3[CH:17]=[CH:16][CH:15]=[C:14]([C:18]([F:19])([F:21])[F:20])[C:13]=3[CH3:22])[C:6]=2[CH:5]=[C:4]([N:24]2[CH2:30][CH2:29][O:28][CH2:27][CH2:26]2)[CH:3]=1

Participants

6

Reactant 3

HCID 21521Bis(2-bromoethyl) etherHCID 81531DiisopropylethylamineHCID 866878174-bromo-2-methyl-1-(2-methyl-3-(trifluoromethyl)benzyl)-1H-benzo[d]imidazol-6-amine

Product 1

HCID 569605424-(7-bromo-2-methyl-3-(2-methyl-3-(trifluoromethyl)benzyl)-3H-benzo[d]imidazol-5-yl)morpholineYield 79.4%

Reagents, catalysts & solvents 2

HCID 174Ethylene GlycolSolventHCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 7-bromo-2-methyl-3-(2-methyl-3-(trifluoromethyl)benzyl)-3H-benzo[d]imidazol-5-amine (45 g, 113 mmol), 1-bromo-2-(2-bromoethoxy)ethane (39 g, 169 mmol) and DIPEA (21 g, 169 mmol) in ethylene glycol (700 mL) was stirred at 100° C. for 20 h. It was cooled to rt, and diluted with water (300 mL) and extracted with DCM (300 mL×4). The combined organic layers were washed with brine, dried over sodium sulphate and evaporated. The residue was combined with previous batch prepared similarly and purified by column chromatography (eluted with petroleum ether/ethyl acetate=1/1) to give the product (42 g, 55%) as a yellow solid; LC/MS: MS (ES+) m/e 468 [M+H]+; 1H NMR (300 MHz, DMSO-d6) δ ppm 2.36 (s, 3H), 2.53 (s, 3H), 3.06 (t, J=4.5 Hz, 4H), 3.70 (t, J=4.5 Hz, 4H), 5.53 (s, 2H), 6.32 (d, J=7.8 Hz, 1H), 6.99 (d, J=1.5 Hz, 1H), 7.10 (d, J=1.5 Hz, 1H), 7.25 (t, J=7.8 Hz, 1H), 7.61 (d, J=7.8 Hz, 1H).

Workup

  1. temperatureIt was cooled to rt
  2. extractionextracted with DCM (300 mL×4)
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over sodium sulphate
  5. customevaporated
  6. customprepared similarly
  7. custompurified by column chromatography (eluted with petroleum ether/ethyl acetate=1/1)

Sources & evidence

ORD record
ord-ffaf2a0abeee4f9e8fee697ffb3f5768
Source dataset
uspto-grants-2014_07
Patent number
US08778937B2

Reaction notes

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