Imidazole → HCID 178462126, compound

HRID 1944759Notes

Reaction equation

HRID 1944759 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]([NH:10][C:11]([C@H:13]2[CH2:18][CH2:17][C@H:16]([NH:19][S:20]([C:23]3[CH:28]=[CH:27][C:26](Br)=[CH:25][CH:24]=3)(=[O:22])=[O:21])[CH2:15][CH2:14]2)=[O:12])[CH3:9])=[CH:4][CH:3]=1.[NH:30]1[CH:34]=[CH:33][N:32]=[CH:31]1.C([O-])([O-])=O.[Cs+].[Cs+]>[Cu]>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]([NH:10][C:11]([C@H:13]2[CH2:18][CH2:17][C@H:16]([NH:19][S:20]([C:23]3[CH:28]=[CH:27][C:26]([N:30]4[CH:34]=[CH:33][N:32]=[CH:31]4)=[CH:25][CH:24]=3)(=[O:22])=[O:21])[CH2:15][CH2:14]2)=[O:12])[CH3:9])=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 795ImidazoleHCID 10796Cesium carbonateHCID 178462119HCID 178462119, compound

Product 1

HCID 178462126HCID 178462126, compoundYield 8.1%

Reagents, catalysts & solvents 1

HCID 23978CopperCatalyst

Procedure

Trans-4-(4-Bromo-benzenesulfonylamino)-cyclohexanecarboxylic acid [(R)-1-(4-fluoro-phenyl)-ethyl]-amide (Example 115, 80 mg, 0.166 mmol), imidazole (14 mg, 0.199 mmol), polyethylene glycol (30 mg), Cs2CO3 (76 mg, 0.232 mmol), and Copper II oxide (2 mg, 0.01 mmol) were weighed into a microwave vial. The vial was flushed with N2, NMP was added and the reaction mixture was microwaved at 200° C. After 20 min. the reaction mixture was diluted with EtOAc (50 ml) and filtered through celite. The filtrate was concentrated in vacuo and the residue was passed through a 25+S biotage column with an isocratic gradient of 10% MeOH in EtOAc. Product fractions combined and concentrated. The crude product was repurified via reverse phase chromatography on prep-HPLC (150 mm, C8 luna, 15-20 min run, 10%-100% MeCN in water containing 0.1% TFA) and the fractions containing the product were lyophilized to yield the title compound as a white solid (6.3 mg). MS MH+ 471.1

Workup

  1. customThe vial was flushed with N2, NMP
  2. additionwas added
  3. customthe reaction mixture was microwaved at 200° C
  4. additionAfter 20 min. the reaction mixture was diluted with EtOAc (50 ml)
  5. filtrationfiltered through celite
  6. concentrationThe filtrate was concentrated in vacuo
  7. concentrationconcentrated
  8. customThe crude product was repurified via reverse phase chromatography on prep-HPLC (150 mm, C8 luna, 15-20 min run, 10%-100% MeCN in water containing 0.1% TFA)
  9. additionthe fractions containing the product

Sources & evidence

ORD record
ord-211f472cc290458a992dcf00181e64e0
Source dataset
uspto-grants-2013_03
Patent number
US08394858B2

Reaction notes

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