Potassium Carbonate → 6-Fluoro-3-[(3-{[(4-fluorophenyl)sulfonyl]methyl}azetidin-1-yl)methyl]-1,2-benzisothiazole Hydrochloride

HRID 10209ノート

反応式

HRID 10209 の反応式
Br[CH2:2][C:3]1[C:7]2[CH:8]=[CH:9][C:10]([F:12])=[CH:11][C:6]=2[S:5][N:4]=1.[ClH:13].[F:14][C:15]1[CH:20]=[CH:19][C:18]([S:21]([CH2:24][CH:25]2[CH2:28][NH:27][CH2:26]2)(=[O:23])=[O:22])=[CH:17][CH:16]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.[OH-].[Na+]>[ClH:13].[F:12][C:10]1[CH:9]=[CH:8][C:7]2[C:3]([CH2:2][N:27]3[CH2:28][CH:25]([CH2:24][S:21]([C:18]4[CH:19]=[CH:20][C:15]([F:14])=[CH:16][CH:17]=4)(=[O:23])=[O:22])[CH2:26]3)=[N:4][S:5][C:6]=2[CH:11]=1

参加物

6

反応物 3

HCID 11430Potassium CarbonateHCID 219783933-{[(4-Fluorophenyl)sulfonyl]methyl}azetidine hydrochlorideHCID 219784071,2-Benzisothiazole, 3-(bromomethyl)-6-fluoro-

生成物 1

HCID 116044116-Fluoro-3-[(3-{[(4-fluorophenyl)sulfonyl]methyl}azetidin-1-yl)methyl]-1,2-benzisothiazole Hydrochloride収率 23.2%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 14798Sodium Hydroxide溶媒

実験手順

3-Bromomethyl-6-fluoro-1,2-benzisothiazole (73 mg, 0.3 mmol) was added to a mixture of 3-{[(4-fluorophenyl)sulfonyl]methyl}azetidine hydrochloride (57 mg, 0.21 mmol) and potassium carbonate (91 mg, 0.66 mmol) in DMF (2 mL) and the resulting mixture stirred at room temperature for 18 h. The mixture was diluted with 0.5M sodium hydroxide solution (20 mL) and extracted with EtOAc (2×10 mL). The organic extracts were washed with saturated brine (10 mL), combined, dried (MgSO4) and concentrated. The residue was purified by preparative thin layer chromatography, eluting with 2.5% MeOH/DCM, to afford an oil which crystallised on standing (35 mg, 41%). The solid was dissolved in EtOAc, the resulting solution heated and treated with 1M HCl in diethyl ether (0.11 mL). The mixture was allowed to cool to give a crystalline solid which was collected under suction to afford the title compound (21 mg). 1H NMR (400 MHz, CD3OD) δ 3.33–3.41 (1H, m), 3.72 (2H, d, J=7.6 Hz), 4.23–4.28 (2H, m), 4.44–4.49 (2H, m), 4.96 (2H, s), 7.35–7.46 (3H, m), 7.87–7.90 (1H, m), 7.99–8.04 (2H, m), 8.10–8.13 (1H, m). (471 MHz, CD3OD)δF −105.2, −112.7. m/z (ES+) 395 (M+H)+.

後処理

  1. extractionextracted with EtOAc (2×10 mL)
  2. washThe organic extracts were washed with saturated brine (10 mL)
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated
  5. customThe residue was purified by preparative thin layer chromatography
  6. washeluting with 2.5% MeOH/DCM
  7. customto afford an oil which
  8. customcrystallised
  9. dissolutionThe solid was dissolved in EtOAc
  10. temperaturethe resulting solution heated
  11. additiontreated with 1M HCl in diethyl ether (0.11 mL)
  12. temperatureto cool
  13. customto give a crystalline solid which
  14. customwas collected under suction

出典と根拠

ORDレコード
ord-07009c0944cf4a4698a88d07fc9fee5f
出典データセット
uspto-grants-2006_08
特許番号
US07094777B2

反応ノート

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