Sodium Carbonate → 4-(2-furanyl)-2-methyl-1-{[2-methyl-3-(trifluoromethyl)phenyl]methyl}-6-(4-morpholinyl)-1H-benzimidazole

HRID 44561Notes

Reaction equation

HRID 44561 reaction equation
Br[C:2]1[C:10]2[N:9]=[C:8]([CH3:11])[N:7]([CH2:12][C:13]3[CH:18]=[CH:17][CH:16]=[C:15]([C:19]([F:22])([F:21])[F:20])[C:14]=3[CH3:23])[C:6]=2[CH:5]=[C:4]([N:24]2[CH2:29][CH2:28][O:27][CH2:26][CH2:25]2)[CH:3]=1.[O:30]1[CH:34]=[CH:33][CH:32]=[C:31]1B(O)O.C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl>[O:30]1[CH:34]=[CH:33][CH:32]=[C:31]1[C:2]1[C:10]2[N:9]=[C:8]([CH3:11])[N:7]([CH2:12][C:13]3[CH:18]=[CH:17][CH:16]=[C:15]([C:19]([F:22])([F:20])[F:21])[C:14]=3[CH3:23])[C:6]=2[CH:5]=[C:4]([N:24]2[CH2:29][CH2:28][O:27][CH2:26][CH2:25]2)[CH:3]=1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 2734357Furan-2-boronic acidHCID 569605424-(7-bromo-2-methyl-3-(2-methyl-3-(trifluoromethyl)benzyl)-3H-benzo[d]imidazol-5-yl)morpholine

Product 1

HCID 569609594-(2-furanyl)-2-methyl-1-{[2-methyl-3-(trifluoromethyl)phenyl]methyl}-6-(4-morpholinyl)-1H-benzimidazoleYield 24.43%

Reagents, catalysts & solvents 3

HCID 178418807HCID 178418807, compoundCatalystHCID 962WaterSolvent2×HCID 80711,2-DimethoxyethaneSolvent

Procedure

A mixture of 4-bromo-2-methyl-1-{[2-methyl-3-(trifluoromethyl)phenyl]methyl}-6-(4-morpholinyl)-1H-benzimidazole, prepared as described in Example 62 (200 mg, 0.427 mmol), 2-furanyl-boronic acid (71.7 mg, 0.641 mmol), PdCl2(dppf)-CH2Cl2 adduct (34.9 mg, 0.043 mmol) and sodium carbonate (91 mg, 0.854 mmol) in 1,2-Dimethoxyethane (DME) (2.5 mL) and Water (0.5 mL) was irradiated in a microwave reactor for 1 h at 100° C. The mixture was poured into water and extracted with EtOAc. The organic phase was washed with brine, dried over Na2SO4 and evaporated. The residue was purified by RP-HPLC (Gilson, 25-65% Acetonitrile in water plus 0.1% TFA) to give the desired product (48.5 mg, 0.104 mmol, 24.43% yield) as a white powder (separation from impurity was difficult. The head of the peak was discarded decreasing the overall yield). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 7.51-7.63 (m, 3H), 7.42 (d, J=2.02 Hz, 1H), 7.12 (t, J=7.83 Hz, 1H), 6.60 (dd, J=3.28, 1.77 Hz, 1H), 6.51 (d, J=7.83 Hz, 1H), 6.49 (d, J=2.02 Hz, 1H), 5.28 (s, 2H), 3.80-3.94 (m, 4H), 3.12-3.22 (m, 4H), 2.56 (s, 3H), 2.53 (s, 3H). MS (ES+) m/e 456.0 [M+H]+.

Workup

  1. customprepared
  2. customwas irradiated in a microwave reactor for 1 h at 100° C
  3. extractionextracted with EtOAc
  4. washThe organic phase was washed with brine
  5. dry with materialdried over Na2SO4
  6. customevaporated
  7. customThe residue was purified by RP-HPLC (Gilson, 25-65% Acetonitrile in water plus 0.1% TFA)

Sources & evidence

ORD record
ord-f92df1de9e854fda9534dbd82dd86ad1
Source dataset
uspto-grants-2013_09
Patent number
US08541411B2

Reaction notes

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