Pyridine → HCID 44177180, compound

HRID 1673023Notes

Reaction equation

HRID 1673023 reaction equation
[Cl:1][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[C:16]1[C:21]([Cl:22])=[CH:20][CH:19]=[CH:18][C:17]=1[Cl:23].C(Cl)(=O)C(Cl)=O.[C:40](=[N:43]O)([NH2:42])[CH3:41].N1C=CC=CC=1>CN(C=O)C.CCOC(C)=O.C(Cl)(Cl)Cl>[Cl:1][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]2[O:14][N:43]=[C:40]([CH3:41])[N:42]=2)[N:10]=[C:9]1[C:16]1[C:17]([Cl:23])=[CH:18][CH:19]=[CH:20][C:21]=1[Cl:22]

Participants

8

Reactant 4

HCID 1049PyridineHCID 30926N-HydroxyacetamidineHCID 65578Oxalyl chlorideHCID 59240086HCID 59240086, compound

Product 1

HCID 44177180HCID 44177180, compoundYield 18.7%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 6212ChloroformSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a 100 mL round bottom flask was added 1-(3-Chloro-3′-methanesulfonyl-biphenyl-4-yl)-2-(2,6-dichloro-phenyl)-1H-imidazole-4-carboxylic acid (1.01 g, 1.93 mmol) and anhydrous CHCl3 (17 mL). The reaction solution was cooled to 0° C. prior to addition of oxalyl chloride (0.90 mL, 9.70 mmol) and 1 drop of anhydrous DMF. The reaction solution was allowed to stir warming to r.t. over 1.5 h. The solution was concentrated in vacuo and the residue was dissolved anhydrous toluene (19 mL). To the reaction flask was added acetamide oxime (286 mg, 3.86 mmol) and pyridine (470 μL, 5.79 mmol). The reaction solution was allowed to reflux under N2 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 80% EtOAc gradient to yield 202 mg (18% yield) of title compound. MS (ESI) 559.0, 561.0, 563.2 [M+H]+; 1H NMR (400 MHz, DMSO-d6) δ 8.80 (s, 1H), 8.24 (t, J=2 Hz, 1H), 8.19 (d, J=2 Hz, 1H), 8.11 (d, J=8 Hz, 1H), 7.96 (d, J=8 Hz, 1H), 7.85 (dd, J=2 Hz, J2=8 Hz), 7.76 (t, J=8 Hz, 1H), 7.51-7.64 (m, 3H), 7.46 (d, J=8 Hz, 1H), 3.31 (s, 3H), 2.43 (s, 3H).

Workup

  1. temperaturewarming to r.t. over 1.5 h
  2. concentrationThe solution was concentrated in vacuo
  3. dissolutionthe residue was dissolved anhydrous toluene (19 mL)
  4. temperatureto reflux under N2 for 16 hrs
  5. washwashed
  6. dry with materialThe organic phase was dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customchromatographed through a 25 g SiO2 column

Sources & evidence

ORD record
ord-51463d8c81484825a8540a35b704057a
Source dataset
uspto-grants-2011_08
Patent number
US07998995B2

Reaction notes

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