2,6-Difluorobenzaldehyde → 1-Isopropylsulfonyl-2-amino-6-(2-(2,6-difluorophenyl)-5-(phenyl)-oxazol-4-yl)-benzimidazole

HRID 2252065Notes

Reaction equation

HRID 2252065 reaction equation
[CH:1]([S:4]([N:7]1[C:11]2[CH:12]=[C:13]([C:16](=O)[CH:17]([O:24][Si](C(C)(C)C)(C)C)[C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[CH:14]=[CH:15][C:10]=2[N:9]=[C:8]1[NH2:33])(=[O:6])=[O:5])([CH3:3])[CH3:2].C([O-])(=O)C.[NH4+:38].[F:39][C:40]1[CH:47]=[CH:46][CH:45]=[C:44]([F:48])[C:41]=1[CH:42]=O.[NH4+].[Cl-].[NH4+].[OH-]>C(O)(=O)C.O.C([O-])(=O)C.[Cu+]>[CH:1]([S:4]([N:7]1[C:11]2[CH:12]=[C:13]([C:16]3[N:38]=[C:42]([C:41]4[C:40]([F:39])=[CH:47][CH:46]=[CH:45][C:44]=4[F:48])[O:24][C:17]=3[C:18]3[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=3)[CH:14]=[CH:15][C:10]=2[N:9]=[C:8]1[NH2:33])(=[O:6])=[O:5])([CH3:2])[CH3:3]

Participants

8

Reactant 4

HCID 1362842,6-DifluorobenzaldehydeHCID 517165Ammonium AcetateHCID 11340754HCID 11340754, compoundHCID 21863491Ammonium chloride ammonium hydroxide

Product 1

HCID 179816261-Isopropylsulfonyl-2-amino-6-(2-(2,6-difluorophenyl)-5-(phenyl)-oxazol-4-yl)-benzimidazoleYield 11%

Reagents, catalysts & solvents 3

HCID 69023Cuprous acetateCatalystHCID 176Acetic AcidSolventHCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 1-isopropylsulfonyl-2-amino-6-(α-((tert-butyldimethylsilyl)oxy)-α-(phenyl)acetyl)-benzimidazole (5.84 g, 12.0 mmol) in acetic acid (glacial, 100 mL) add ammonium acetate (9.26 g, 120 mmol) and copper (I) acetate (4.31 g, 23.7 mmol), followed by 2,6-difluorobenzaldehyde (1.41 mL, 13.1 mmol), and stir the mixture at 100° C. for 4 hours. Cool the mixture to 0° C. and slowly pour over a mixture of NH4Cl/NH4OH 3:1, pH=9. Dilute the mixture with H2O (200 mL), extract with EtOAc (3×200 mL), wash with saturated aqueous NaCl (150 mL), dry (Na2SO4), and concentrate in vacuo. Purify the residue in a biotage system (eluent:CH2Cl2/MeCN 5:1), and then by HPLC, to afford a yellow solid, 675 mg, 11% yield. MS(ES+): m/z=495.0 (M+H)+

Workup

  1. temperatureCool the mixture to 0° C.
  2. extractionextract with EtOAc (3×200 mL)
  3. washwash with saturated aqueous NaCl (150 mL)
  4. dry with materialdry (Na2SO4)
  5. concentrationconcentrate in vacuo
  6. customPurify the residue in a biotage system (eluent:CH2Cl2/MeCN 5:1)
  7. customby HPLC, to afford a yellow solid, 675 mg, 11% yield

Sources & evidence

ORD record
ord-9a939b2cb85a487c8f4a15b9825ce65d
Source dataset
uspto-grants-2008_01
Patent number
US07320995B2

Reaction notes

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