Potassium Carbonate → HCID 67337246, compound

HRID 1673034Notes

Reaction equation

HRID 1673034 reaction equation
Cl[C:2]1[CH:3]=[C:4]([C:24]2[CH:29]=[CH:28][CH:27]=[C:26]([S:30]([CH3:33])(=[O:32])=[O:31])[CH:25]=2)[CH:5]=[CH:6][C:7]=1[N:8]1[CH:12]=[C:11]([C:13](O)=[O:14])[N:10]=[C:9]1[CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1[Cl:23].BrC1C=CC([N:41]2C=C(C(O)=O)[N:43]=[C:42]2[C:49]2C=CC=CC=2Cl)=C(Cl)C=1.C(Cl)(=O)C(Cl)=O.C(=NO)(N)C.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C.CCOC(C)=O.C1(C)C(C)=CC=CC=1.C(Cl)(Cl)Cl>[CH3:33][S:30]([C:26]1[CH:25]=[C:24]([C:4]2[CH:5]=[CH:6][C:7]([N:8]3[CH:12]=[C:11]([C:13]4[O:14][N:43]=[C:42]([CH3:49])[N:41]=4)[N:10]=[C:9]3[CH2:16][C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[Cl:23])=[CH:2][CH:3]=2)[CH:29]=[CH:28][CH:27]=1)(=[O:31])=[O:32]

Participants

10

Reactant 5

HCID 11430Potassium CarbonateHCID 30926N-HydroxyacetamidineHCID 65578Oxalyl chlorideHCID 59240289HCID 59240289, compoundHCID 67337145HCID 67337145, compound

Product 1

HCID 67337246HCID 67337246, compoundYield 31%

Reagents, catalysts & solvents 4

HCID 6228DimethylformamideCatalystHCID 6212ChloroformSolventHCID 7237O-XyleneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a 100 mL round bottom flask was added 1-(3-Chloro-3′-methanesulfonylbiphenyl-4-yl)-2-(2-chlorobenzyl)-1H-imidazole-4-carboxylic acid, obtained in a manner similar to that described for 1-(4-Bromo-2-chloro-phenyl)-2-(2-chlorophenyl)-1H-imidazole-4-carboxylic acid in Example BB1 (350 mg, 707 μmol) and anhydrous CHCl3 (15 mL). The reaction solution was cooled to 0° C. prior to addition of oxalyl chloride (310 μL, 3.54 mmol) and 1 drop of anhydrous DMF. The reaction solution was allowed to stir warming to room temperature over 1.5 h. The solution was concentrated in vacuo and the residue was dissolved in anhydrous 1,4-dioxane (20 mL). To the reaction flask was added acetamide oxime (104 mg, 1.41 mmol) and K2CO3 (293 mg, 2.12 mmol). The mixture was stirred at room temperature for 1 hr prior to addition of xylene (43 mL) and raising the reaction temperature to reflux for 16 hrs. The reaction solution was diluted with EtOAc (100 mL) and washed with sat aq. NH4Cl (150 mL×2). The organic phase was dried over Na2SO4, filtered, concentrated in vacuo, and chromatographed through a 25 g SiO2 column using a 100% hexane to 100% EtOAc gradient to yield 115 mg (31% yield) of title compound. MS (ESI) 533.3, 535.3 [M+H]+; 1H NMR (400 MHz, DMSO-d6) δ 8.16 (s, 1H), 8.06 (s, 1H), 7.97 (d, J=7.6 Hz, 1H), 7.91 (d, J=7.6 Hz, 1H), 7.76 (t, J=7.6 Hz, 1H), 7.50 (d, J=8.4 Hz, 2H), 7.26 (dd, J=7.8 Hz, J2=1 Hz, 1H), 7.12 (d, J=8.4 Hz, 2H), 7.09 (m, 1H), 7.02 (dd, J=7.8 Hz, J2=1 Hz, 1H), 6.95 (t, J=8 Hz, 1H), 3.32 (s, 3H), 2.39 (s, 3H), 1.79 (s, 3H).

Workup

  1. customobtained in a manner similar to
  2. temperaturewarming to room temperature over 1.5 h
  3. concentrationThe solution was concentrated in vacuo
  4. dissolutionthe residue was dissolved in anhydrous 1,4-dioxane (20 mL)
  5. stirringThe mixture was stirred at room temperature for 1 hr
  6. temperatureraising the reaction temperature
  7. temperatureto reflux for 16 hrs
  8. washwashed
  9. dry with materialThe organic phase was dried over Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customchromatographed through a 25 g SiO2 column

Sources & evidence

ORD record
ord-e589fbf5330945b098d56ce37d5d6157
Source dataset
uspto-grants-2011_08
Patent number
US07998995B2

Reaction notes

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