Oxalic Acid → 1-(3,9-Dimethyl-2,3,4,5-tetrahydroazepino[4,5-b]indol-6(1H)-yl)-2-(4-fluorophenyl) propan-2-ol

HRID 1481416ノート

反応式

HRID 1481416 の反応式
[H-].[Na+].[CH3:3][N:4]1[CH2:17][CH2:16][C:15]2[C:14]3[CH:13]=[C:12]([CH3:18])[CH:11]=[CH:10][C:9]=3[NH:8][C:7]=2[CH2:6][CH2:5]1.[F:19][C:20]1[CH:25]=[CH:24][C:23]([C:26]2([CH3:29])[CH2:28][O:27]2)=[CH:22][CH:21]=1.C(O)(=O)C(O)=O>CN(C=O)C.C1COCC1.O>[F:19][C:20]1[CH:21]=[CH:22][C:23]([C:26]([OH:27])([CH3:28])[CH2:29][N:8]2[C:9]3[CH:10]=[CH:11][C:12]([CH3:18])=[CH:13][C:14]=3[C:15]3[CH2:16][CH2:17][N:4]([CH3:3])[CH2:5][CH2:6][C:7]2=3)=[CH:24][CH:25]=1

参加物

8

反応物 4

HCID 971Oxalic AcidHCID 24758Sodium hydrideHCID 178694862-(4-Fluorophenyl)-2-methyloxiraneHCID 685600921,2,3,4,5,6-Hexahydro-3,9-dimethylazepino[4,5-b]indole

生成物 1

HCID 593683271-(3,9-Dimethyl-2,3,4,5-tetrahydroazepino[4,5-b]indol-6(1H)-yl)-2-(4-fluorophenyl) propan-2-ol

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

The title compound was prepared by following general procedure 5. To a stirred suspension of sodium hydride (67 mg, 0.28 mmol) in 5 mL of DMF, 3,9-dimethyl-1,2,3,4,5,6-hexahydroazepino[4,5-b]indole (0.2 g, 0.934 mmol) was added and stirred at RT for 5 min. 2-(4-Fluorophenyl)-2-methyloxirane (212 mg, 1.39 mmol) was added slowly dropwise and stirred at RT for 14 h. The reaction was monitored by TLC and LCMS. After completion of the reaction, water was added, extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, evaporated under reduced pressure and purified by column chromatography using 10% methanol-DCM. The freebase (30 mg, 0.082 mmol) was dissolved in THF (1.0 mL) and oxalic acid (10 mg, 0.082 mmol) in THF (1.0 mL) was added slowly, the mixture was stirred at RT for 20 min. and the formed solid was filtered, washed with ether and dried to afford the product as oxalate salt (15 mg, brown solid).

後処理

  1. additionwas added
  2. stirringstirred at RT for 14 h
  3. additionwas added
  4. extractionextracted with ethyl acetate
  5. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  6. customevaporated under reduced pressure
  7. custompurified by column chromatography
  8. dissolutionThe freebase (30 mg, 0.082 mmol) was dissolved in THF (1.0 mL)
  9. stirringthe mixture was stirred at RT for 20 min.
  10. filtrationthe formed solid was filtered
  11. washwashed with ether
  12. customdried

出典と根拠

ORDレコード
ord-b243173635094a26b5fd541f25a8dac7
出典データセット
uspto-grants-2016_08
特許番号
US09409910B2

反応ノート

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