HCID 86663953, compound → 1-[2-methyl-6-(4-morpholinyl)-1-(1-naphthalenylmethyl)-1H-benzimidazol-4-yl]ethanone

HRID 2174784Notes

Reaction equation

HRID 2174784 reaction equation
CN(OC)[C:3]([C:5]1[C:13]2[N:12]=[C:11]([CH3:14])[N:10]([CH2:15][C:16]3[C:25]4[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=4)[CH:19]=[CH:18][CH:17]=3)[C:9]=2[CH:8]=[C:7]([N:26]2[CH2:31][CH2:30][O:29][CH2:28][CH2:27]2)[CH:6]=1)=[O:4].[CH3:34][Mg]Cl>O1CCCC1>[CH3:14][C:11]1[N:10]([CH2:15][C:16]2[C:25]3[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=3)[CH:19]=[CH:18][CH:17]=2)[C:9]2[CH:8]=[C:7]([N:26]3[CH2:27][CH2:28][O:29][CH2:30][CH2:31]3)[CH:6]=[C:5]([C:3](=[O:4])[CH3:34])[C:13]=2[N:12]=1

Participants

4

Reactant 2

HCID 86663953HCID 86663953, compoundHCID 178418332HCID 178418332, compound

Product 1

HCID 569599861-[2-methyl-6-(4-morpholinyl)-1-(1-naphthalenylmethyl)-1H-benzimidazol-4-yl]ethanoneYield 62.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of N,2-dimethyl-N-(methyloxy)-6-(4-morpholinyl)-1-(1-naphthalenylmethyl)-1H-benzimidazole-4-carboxamide (82 mg, 0.184 mmol) in Tetrahydrofuran (THF) (10 mL) was added a 3.0 M solution of methylmagnesium chloride (0.123 mL, 0.369 mmol) in THF at 0° C. The resulting reaction mixture was stirred at 0° C. for 2 h and then quenched very carefully with saturated aqueous ammonium chloride. The mixture was diluted with ethyl acetate (50 mL) and the aqueous phase was extracted with ethyl acetate (50 mL×2). The combined organic phases were washed with brine (50 mL), dried over (MgSO4), and filtered. The solution was concentrated under reduced pressure. The crude product was purified on a silica column (40˜60% EtOAc/Hexane) to give the product (46 mg, 59%). 1H NMR (400 MHz, DMSO-d6) δ ppm 2.47 (s, 3H), 3.00 (s, 3H), 3.02-3.10 (m, 4H), 3.59-3.73 (m, 4H), 6.06 (s, 2H), 6.33 (d, J=6.82 Hz, 1H), 7.21-7.42 (m, 3H), 7.52-7.76 (m, 2H), 7.86 (d, J=8.34 Hz, 1H), 8.02 (d, J=7.33 Hz, 1H), 8.25 (d, 1H). MS (ES+) m/e 399.9[M+H]+.

Workup

  1. customThe resulting reaction mixture
  2. customquenched very carefully with saturated aqueous ammonium chloride
  3. additionThe mixture was diluted with ethyl acetate (50 mL)
  4. extractionthe aqueous phase was extracted with ethyl acetate (50 mL×2)
  5. washThe combined organic phases were washed with brine (50 mL)
  6. dry with materialdried over (MgSO4)
  7. filtrationfiltered
  8. concentrationThe solution was concentrated under reduced pressure
  9. customThe crude product was purified on a silica column (40˜60% EtOAc/Hexane)

Sources & evidence

ORD record
ord-464a5716714e44d29f900645f7d16320
Source dataset
uspto-grants-2015_06
Patent number
US09062003B2

Reaction notes

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