Tetrahydrofuran → 3-[4-(1-benzyl-2-methyl-1H-benzimidazol-4-yl)phenyl]-1-{[2-(trimethylsilyl)ethoxy]methyl}-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one

HRID 1044148Notes

Reaction equation

HRID 1044148 reaction equation
[CH2:1]([N:8]1[C:12]2[CH:13]=[CH:14][CH:15]=[C:16](Br)[C:11]=2[N:10]=[C:9]1[CH3:18])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CC1(C)C(C)(C)OB([C:27]2[CH:32]=[CH:31][C:30]([N:33]3[C:37]4=[N:38][CH:39]=[CH:40][CH:41]=[C:36]4[N:35]([CH2:42][O:43][CH2:44][CH2:45][Si:46]([CH3:49])([CH3:48])[CH3:47])[C:34]3=[O:50])=[CH:29][CH:28]=2)O1.C(=O)([O-])[O-].[Na+].[Na+].C1COCC1>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O>[CH2:1]([N:8]1[C:12]2[CH:13]=[CH:14][CH:15]=[C:16]([C:27]3[CH:32]=[CH:31][C:30]([N:33]4[C:37]5=[N:38][CH:39]=[CH:40][CH:41]=[C:36]5[N:35]([CH2:42][O:43][CH2:44][CH2:45][Si:46]([CH3:48])([CH3:47])[CH3:49])[C:34]4=[O:50])=[CH:29][CH:28]=3)[C:11]=2[N:10]=[C:9]1[CH3:18])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 8028TetrahydrofuranHCID 10340Sodium CarbonateHCID 585773473-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-1-{[2-(trimethylsilyl)ethoxy]methyl}-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-oneHCID 671269161-benzyl-4-bromo-2-methyl-1H-benzo[d]imidazole

Product 1

HCID 585773783-[4-(1-benzyl-2-methyl-1H-benzimidazol-4-yl)phenyl]-1-{[2-(trimethylsilyl)ethoxy]methyl}-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-oneYield 53.5%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent2×

Conditions

Temperature
100 °C

Procedure

Benzyl chloride (1.527 mL) was added to a solution of 4-bromo-2-methyl-1H-benzimidazole (1.40 g) and sodium hydride (0.531 g) in DMF (10 ml) at 0° C. The mixture was stirred at room temperature under a dry atmosphere for 1 h. The reaction mixture was diluted with MeOH and concentrated in vacuo. The residue was purified by column chromatography (NH silica gel, eluted with 5%-50% EtOAc in hexane) to give 1-benzyl-4-bromo-2-methyl-1H-benzo[d]imidazole (1.88 g) as tan oil. The mixture of 1-benzyl-4-bromo-2-methyl-1H-benzo[d]imidazole (496 mg), 3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-1-{[2-(trimethylsilyl)ethoxy]methyl}-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one (700 mg), Pd(Ph3P)4 (87 mg), sodium carbonate (476 mg) and THF (18 mL)-water (0.90 mL) was heated at 100° C. for 1 h under microwave irradiation. The mixture was poured into water at room temperature and extracted with EtOAc. The organic layer was separated, washed with brine, dried over MgSO4 and concentrated in vacuo. The residue was purified by column chromatography (silica gel, eluted with 10%-50% EtOAc in hexane) to give 3-[4-(1-benzyl-2-methyl-1H-benzimidazol-4-yl)phenyl]-1-{[2-(trimethylsilyl)ethoxy]methyl}-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one (450 mg) as white crystals.

Workup

  1. extractionextracted with EtOAc
  2. customThe organic layer was separated
  3. washwashed with brine
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by column chromatography (silica gel, eluted with 10%-50% EtOAc in hexane)

Sources & evidence

ORD record
ord-b3f5c92f92cb404083b99f56ea45884a
Source dataset
uspto-grants-2013_10
Patent number
US08563575B2

Reaction notes

Loading…