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 1627277노트

반응식

HRID 1627277 반응식
[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

참가 물질

10

반응물 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

생성물 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)benzenesulfonamide수율 30.7%

시약·촉매·용매 2

HCID 887Methanol용매HCID 6228Dimethylformamide용매

실험 절차

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)+.

후처리

  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)

출처 및 근거

ORD 기록
ord-c9bee8bfe1f940cb89a2d249be8b0602
출처 데이터셋
uspto-grants-2014_07
특허 번호
US08785488B2

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