Sodium Carbonate → (8aS)-2-{[3-({4-[bis(4-fluorophenyl)methyl]piperazin-1-yl}carbonyl)phenyl]sulfonyl}octahydropyrrolo[1,2-a]pyrazine

HRID 400517

反応式

HRID 400517 の反応式
Cl[S:2]([C:5]1[CH:6]=[C:7]([CH:11]=[CH:12][CH:13]=1)[C:8](Cl)=[O:9])(=[O:4])=[O:3].[F:14][C:15]1[CH:20]=[CH:19][C:18]([CH:21]([C:28]2[CH:33]=[CH:32][C:31]([F:34])=[CH:30][CH:29]=2)[N:22]2[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]2)=[CH:17][CH:16]=1.C(=O)([O-])[O-].[Na+].[Na+].[CH2:41]1[NH:46][CH2:45][CH2:44][N:43]2[CH2:47][CH2:48][CH2:49][C@@H:42]12>ClCCl.CO>[F:34][C:31]1[CH:32]=[CH:33][C:28]([CH:21]([C:18]2[CH:17]=[CH:16][C:15]([F:14])=[CH:20][CH:19]=2)[N:22]2[CH2:23][CH2:24][N:25]([C:8]([C:7]3[CH:6]=[C:5]([S:2]([N:46]4[CH2:45][CH2:44][N:43]5[CH2:47][CH2:48][CH2:49][C@H:42]5[CH2:41]4)(=[O:4])=[O:3])[CH:13]=[CH:12][CH:11]=3)=[O:9])[CH2:26][CH2:27]2)=[CH:29][CH:30]=1

参加物

7

反応物 4

HCID 10340Sodium CarbonateHCID 77671Benzoyl chloride, 3-(chlorosulfonyl)-HCID 1529321-(Bis(4-fluorophenyl)methyl)piperazineHCID 781249(6S)-1,4-Diazabicyclo(4.3.0)nonane

生成物 1

HCID 46852288(8aS)-2-{[3-({4-[bis(4-fluorophenyl)methyl]piperazin-1-yl}carbonyl)phenyl]sulfonyl}octahydropyrrolo[1,2-a]pyrazine

試薬・触媒・溶媒 2

HCID 887Methanol溶媒HCID 6344Dichloromethane溶媒2 回

実験手順

To 3-(chlorosulfonyl)benzoyl chloride (0.474 g, 1.981 mmol) in anhydrous dichloromethane (40 mL) was added 1-(bis(4-fluorophenyl)methyl)piperazine (0.571 g, 1.981 mmol) in dichloromethane (4 mL) slowly over 10 minutes at room temperature. Then sodium carbonate (0.64 g, 6 mmol) was added. The mixture was stirred at room temperature overnight. Then (S)-octahydropyrrolo[1,2-a]pyrazine (0.250 g, 1.981 mmol) was added. The mixture was stirred at reflux for 20 minutes and then at room temperature for 3 days. Methanol (5 mL) was added, the mixture was stirred for 20 minutes, then filtered, and concentrated. The residue was purified by chromatography on silica gel (ethyl acetate/methanol=20:1) to give the titled compound: 1H NMR (400 MHz, DMSO-d6) δ ppm 1.07 (m, 1H), 1.55 (m, 2H), 1.71 (m, 1H), 1.95 (m, 4H), 2.08 (m, 1H), 2.28 (m, 3H), 2.39 (m, 3H), 2.85 (m, 1H), 2.92 (m, 1H), 3.57 (m, 2H), 3.74 (m, 2H), 4.45 (s, 1H), 7.13 (m, 4H), 7.45 (m, 4H), 7.66 (s, 1H), 7.70 (m, 2H), 7.80 (m, 1H); MS (ESI) m/z 581 (M+H)+.

後処理

  1. stirringThe mixture was stirred
  2. temperatureat reflux for 20 minutes
  3. waitat room temperature for 3 days
  4. stirringthe mixture was stirred for 20 minutes
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by chromatography on silica gel (ethyl acetate/methanol=20:1)

出典と根拠

ORDレコード
ord-6884d3706aab415aba36e30f84c19191
出典データセット
uspto-grants-2014_06
特許番号
US08741899B2

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