Potassium Carbonate → HCID 86702226, compound

HRID 83834Notes

Reaction equation

HRID 83834 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([S:35](O)(=[O:37])=[O:36])[CH:5]=[C:6]([F:34])[C:7]=1[CH2:8][S:9][C:10]1[N:11]([C:27]2[CH:32]=[CH:31][C:30]([F:33])=[CH:29][CH:28]=2)[C:12]([C:15]([C:18]2[CH:23]=[CH:22][C:21]([F:24])=[C:20]([O:25][CH3:26])[CH:19]=2)([CH3:17])[CH3:16])=[CH:13][N:14]=1.S(Cl)(Cl)=O.Cl.[Cl-].[NH2:45][CH2:46][CH2:47][C:48]1[CH:49]=[N+:50]([CH3:54])[CH:51]=[CH:52][CH:53]=1.C([O-])([O-])=O.[K+].[K+]>C(Cl)Cl.CC#N.CN(C=O)C>[Cl-:1].[Cl:1][C:2]1[CH:3]=[C:4]([S:35]([NH:45][CH2:46][CH2:47][C:48]2[CH:49]=[N+:50]([CH3:54])[CH:51]=[CH:52][CH:53]=2)(=[O:36])=[O:37])[CH:5]=[C:6]([F:34])[C:7]=1[CH2:8][S:9][C:10]1[N:11]([C:27]2[CH:32]=[CH:31][C:30]([F:33])=[CH:29][CH:28]=2)[C:12]([C:15]([C:18]2[CH:23]=[CH:22][C:21]([F:24])=[C:20]([O:25][CH3:26])[CH:19]=2)([CH3:16])[CH3:17])=[CH:13][N:14]=1

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 24386Thionyl ChlorideHCID 67234778HCID 67234778, compoundHCID 867022273-chloro-5-fluoro-4-((5-(2-(4-fluoro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)benzenesulfonic acid

Product 1

HCID 86702226HCID 86702226, compoundYield 11.3%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
50 °C

Procedure

To a suspension of 3-chloro-5-fluoro-4-((5-(2-(4-fluoro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)benzenesulfonic acid (250 mg, 0.43 mmol) in DCM (5 mL) was added thionyl chloride (1 mL) and DMF (10 uL, anhyd). The reaction mixture was heated 2 h at 50° C., concentrated, diluted with DCM, and concentrated to dryness. The sulfonyl chloride intermediate was diluted with DCM (3 mL) and added slowly to a well-stirred mixture of 3-(2-aminoethyl)-1-methylpyridinium chloride hydrochloride (100 mg, 0.58 mmol) and K2CO3(178 mg, 1.29 mmol) in CH3CN (10 mL). After stirring 2 h, the reaction mixture was filtered and concentrated. The residue was purified by chromatography (10-20% MeOH/DCM) to afford the title compound as a solid (18 mg, 6%). 1H NMR (400 MHz, CDCl3) δ 9.13 (s, 1H), 8.77 (s, 1H), 8.40-8.32 (m, 1H), 8.03 (s, 1H), 7.71 (s, 1H), 7.51 (d, J=8.29 Hz, 1H), 7.15 (s, 1H), 6.96-6.78 (m, 3H), 6.62-6.38 (m, 5H), 4.54 (s, 3H), 4.03 (s, 2H), 3.77 (s, 4H), 3.52-3.41 (m, 4H), 3.22-3.12 (m, 2H), 1.82-1.58 (m, 6H), 1.50 (s, 7H), 1.21 (t, J=7.02 Hz, 4H); MS (EI) m/z 701 [M]+.

Workup

  1. concentrationconcentrated
  2. additiondiluted with DCM
  3. concentrationconcentrated to dryness
  4. additionThe sulfonyl chloride intermediate was diluted with DCM (3 mL)
  5. filtrationthe reaction mixture was filtered
  6. concentrationconcentrated
  7. customThe residue was purified by chromatography (10-20% MeOH/DCM)

Sources & evidence

ORD record
ord-5258a52d257c4192980ff1516c036004
Source dataset
uspto-grants-2014_09
Patent number
US08846739B2

Reaction notes

Loading…