Hydrochloric Acid → 3-Chloro-4-((5-(2-(3,4-dichlorophenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-N-(pyrrolidin-1-ylcarbamoyl)benzenesulfonamide

HRID 1627277Notes

Reaction equation

HRID 1627277 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([S:33]([NH2:36])(=[O:35])=[O:34])[CH:5]=[CH:6][C:7]=1[CH2:8][S:9][C:10]1[N:11]([C:26]2[CH:31]=[CH:30][C:29]([F:32])=[CH:28][CH:27]=2)[C:12]([C:15]([C:18]2[CH:23]=[CH:22][C:21]([Cl:24])=[C:20]([Cl:25])[CH:19]=2)([CH3:17])[CH3:16])=[CH:13][N:14]=1.[OH-].[Na+].[N:39]1([NH:44][C:45](=[O:53])[O:46][C:47]2[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=2)[CH2:43][CH2:42][CH2:41][CH2:40]1.C1(OC(Cl)=O)C=CC=CC=1.NN1CCCC1.Cl>CO.CN(C=O)C>[N:39]1([NH:44][C:45](=[O:53])[O:46][C:47]2[CH:48]=[CH:49][CH:50]=[CH:51][CH:52]=2)[CH2:40][CH2:41][CH2:42][CH2:43]1.[Cl:1][C:2]1[CH:3]=[C:4]([S:33]([NH:36][C:45](=[O:46])[NH:44][N:39]2[CH2:43][CH2:42][CH2:41][CH2:40]2)(=[O:35])=[O:34])[CH:5]=[CH:6][C:7]=1[CH2:8][S:9][C:10]1[N:11]([C:26]2[CH:31]=[CH:30][C:29]([F:32])=[CH:28][CH:27]=2)[C:12]([C:15]([C:18]2[CH:23]=[CH:22][C:21]([Cl:24])=[C:20]([Cl:25])[CH:19]=2)([CH3:17])[CH3:16])=[CH:13][N:14]=1

Participants

10

Reactant 6

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 15891Phenyl chloroformateHCID 279461-PyrrolidinamineHCID 20185956N-(Phenoxycarbonylamino)pyrrolidineHCID 667400293-Chloro-4-((5-(2-(3,4-dichlorophenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)benzenesulfonamide

Product 2

HCID 20185956N-(Phenoxycarbonylamino)pyrrolidineHCID 667403653-Chloro-4-((5-(2-(3,4-dichlorophenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-N-(pyrrolidin-1-ylcarbamoyl)benzenesulfonamideYield 30.7%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of 3-chloro-4-((5-(2-(3,4-dichlorophenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)benzenesulfonamide (76 mg, 0.13 mmol, 1.0 eq) in MeOH (0.5 mL) was added sodium hydroxide (5 mg, 0.13 mmol, 1.0 eq, dissolved in 0.5 mL MeOH). The mixture was stirred at room temperature for 16 h then concentrated in vacuo. The residue was diluted with anhydrous DMF (0.5 mL) and then charged with a solution of phenyl pyrrolidin-1-ylcarbamate (30 mg, 0.14 mmol, 1.1 eq) in 0.5 mL of DMF. Phenyl pyrrolidin-1-ylcarbamate was prepared by treatment of phenychloroformate with 1-aminopyrrolidine. The reaction mixture was then heated at 50° C. overnight. The mixture was cooled, acidified with 1M HCl and extracted with ethyl acetate (3×). The organic layers were washed with brine, dried (magnesium sulfate) and concentrated. Purification by column chromatography (30% methanol/ethyl acetate) provided the title compound (15 mg) as a white foam. 1H NMR (CD2Cl2, 400 MHz): δ 8.98 (br s, 1H), 8.00 (s, 1H), 7.82 (dd, J=8.3, 2.2 Hz, 1H), 7.51 (d, J=8.3 Hz, 1H), 7.27 (d, J=8.3 Hz, 1H), 7.18 (s, 1H), 7.00 (d, J=2.2 Hz, 1H), 6.85-6.78 (m, 4H), 6.32-6.27 (m, 2H), 4.33 (s, 2H), 3.22-3.13 (2H), 2.48-2.38 (m, 2H), 1.86-1.78 (m, 4H), 1.47 (s, 6H); MS (EI) m/z 695 (MH)+.

Workup

  1. concentrationthen concentrated in vacuo
  2. additionThe residue was diluted with anhydrous DMF (0.5 mL)
  3. temperatureThe reaction mixture was then heated at 50° C. overnight
  4. temperatureThe mixture was cooled
  5. extractionextracted with ethyl acetate (3×)
  6. washThe organic layers were washed with brine
  7. dry with materialdried (magnesium sulfate)
  8. concentrationconcentrated
  9. customPurification by column chromatography (30% methanol/ethyl acetate)

Sources & evidence

ORD record
ord-c9bee8bfe1f940cb89a2d249be8b0602
Source dataset
uspto-grants-2014_07
Patent number
US08785488B2

Reaction notes

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