Sodium Carbonate → 1-Isopropylsulfonyl-2-amino-6-(1-(benzyl)-2-(methyl)-5-(2,4-difluorophenyl)-imidazol-4-yl)-benzimidazole

HRID 2252032Notes

Reaction equation

HRID 2252032 reaction equation
[CH2:1]([N:8]1[C:12]([C:13]2[CH:18]=[CH:17][C:16]([F:19])=[CH:15][C:14]=2[F:20])=[C:11](Br)[N:10]=[C:9]1[CH3:22])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH:23]([S:26]([N:29]1[C:33]2[CH:34]=[C:35](B(O)O)[CH:36]=[CH:37][C:32]=2[N:31]=[C:30]1[NH2:41])(=[O:28])=[O:27])([CH3:25])[CH3:24].C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.O>[CH:23]([S:26]([N:29]1[C:33]2[CH:34]=[C:35]([C:11]3[N:10]=[C:9]([CH3:22])[N:8]([CH2:1][C:2]4[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=4)[C:12]=3[C:13]3[CH:18]=[CH:17][C:16]([F:19])=[CH:15][C:14]=3[F:20])[CH:36]=[CH:37][C:32]=2[N:31]=[C:30]1[NH2:41])(=[O:27])=[O:28])([CH3:25])[CH3:24]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 179816721-benzyl-2-methyl bromo-5-(2,4-difluorophenyl)-1H-imidazoleHCID 17981723HCID 17981723, compound

Product 1

HCID 179817511-Isopropylsulfonyl-2-amino-6-(1-(benzyl)-2-(methyl)-5-(2,4-difluorophenyl)-imidazol-4-yl)-benzimidazoleYield 24.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 1-(benzyl)-4-(bromo)-5-(2,4-difluorophenyl)-2-(methyl)-imidazole (1.12 g, 3.08 mmol) in 8 mL DME add 1-isopropylsulfonyl-2-amino-benzimidazole-6-boronic acid (2.62 g, 9.25 mmol) (described in preparation 58). Add sodium carbonate (0.98 g, 9.25 mmol) dissolved in water (1 mL) and trans-dichlorobis(triphenylphosphine) palladium (II) (0.65 g, 0.93 mmol). Heat the mixture to 100° C. with stirring under nitrogen. After 3 hours cool the solution and filter over a pad of Celite and sodium sulfate. Purify the residue by radial chromatography eluting with 3% methanol in CH2Cl2 with a gradient to 10% methanol. Perform a second purification by radial chromatography eluting with 4% methanol in CH2Cl2 with a gradient to 6% methanol to yield 390 mg (24%) of the title compound as a yellow solid. MS(ES+): m/z=522.0 (M+H)+

Workup

  1. temperatureAfter 3 hours cool the solution
  2. filtrationfilter over a pad of Celite and sodium sulfate
  3. customPurify the residue by radial chromatography
  4. washeluting with 3% methanol in CH2Cl2 with a gradient to 10% methanol
  5. customa second purification by radial chromatography
  6. washeluting with 4% methanol in CH2Cl2 with a gradient to 6% methanol

Sources & evidence

ORD record
ord-63b1ffd1cdc7483c9ba863e907fff9f1
Source dataset
uspto-grants-2008_01
Patent number
US07320995B2

Reaction notes

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