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 1627277ノート

反応式

HRID 1627277 の反応式
[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

参加物

10

反応物 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

生成物 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)benzenesulfonamide収率 30.7%

試薬・触媒・溶媒 2

HCID 887Methanol溶媒HCID 6228Dimethylformamide溶媒

実験手順

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)+.

後処理

  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)

出典と根拠

ORDレコード
ord-c9bee8bfe1f940cb89a2d249be8b0602
出典データセット
uspto-grants-2014_07
特許番号
US08785488B2

反応ノート

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