Carbonate Ion → 1-Phenyl-N-{[2-(trifluoromethyl)-2-oxiranyl]methyl}-1H-indazol-4-amine

HRID 551425

反応式

HRID 551425 の反応式
[Bi](Cl)(Cl)Cl.CC1C=CC(S(O[CH2:16][C:17]2([C:20]([F:23])([F:22])[F:21])[CH2:19][O:18]2)(=O)=O)=CC=1.[C:24]1([N:30]2[C:38]3[CH:37]=[CH:36][CH:35]=[C:34]([NH2:39])[C:33]=3[CH:32]=[N:31]2)[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.S([O-])([O-])(=O)=O.[Na+].[Na+].C(=O)([O-])[O-].C(N(CC)C(C)C)(C)C>ClCCl.C(Cl)(Cl)Cl.O1CCCC1>[C:24]1([N:30]2[C:38]3[CH:37]=[CH:36][CH:35]=[C:34]([NH:39][CH2:16][C:17]4([C:20]([F:21])([F:22])[F:23])[CH2:19][O:18]4)[C:33]=3[CH:32]=[N:31]2)[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1

参加物

10

反応物 6

HCID 19660Carbonate IonHCID 24436Sodium SulfateHCID 24591Bismuth trichlorideHCID 81531DiisopropylethylamineHCID 24809749(2-(Trifluoromethyl)oxiran-2-yl)methyl 4-methylbenzenesulfonateHCID 249380571-phenyl-1H-indazol-4-amine

生成物 1

HCID 249380531-Phenyl-N-{[2-(trifluoromethyl)-2-oxiranyl]methyl}-1H-indazol-4-amine収率 56.8%

試薬・触媒・溶媒 3

HCID 6212Chloroform溶媒HCID 6344Dichloromethane溶媒2 回HCID 8028Tetrahydrofuran溶媒

実験手順

Bismuth chloride (623 mg, 1.98 mmol) was added to a suspension of [2-(trifluoromethyl)-2-oxiranyl]methyl 4-methylbenzenesulfonate (5.85 g, 19.76 mmol) and 1-phenyl-1H-indazol-4-amine (4.13 g, 19.76 mmol) in dry dichloromethane (8 ml) and the mixture stirred at room temperature over the weekend. The resulting thick suspension was diluted with dichloromethane and stirred overnight. The mixture was then diluted with chloroform (200 ml) and sodium sulphate (30 g) and polymer supported carbonate resin (Fluka, ca. 3.5 mmoles carbonate/g resin, 11 g) were added and the mixture stirred overnight. LCMS showed no evidence for cyclisation to the target epoxide. Dry tetrahydrofuran (50 ml) and N,N-diisopropylethylamine (0.85 ml, 4.88 mmol) were then added and the mixture stirred overnight when LCMS indicated complete reaction. The mixture was filtered and the filtrate was washed with water. The aqueous phase was back-extracted with dichloromethane and the combined organic phases were dried and evaporated to give crude product which was purified by silica gel chromatography using the Flashmaster II (2×100 g cartridges) eluting with a 0 to 50% dichloromethane:ethyl acetate gradient over 40 minutes to give the title compound (3.74 g).

後処理

  1. stirringstirred overnight
  2. additionwere added
  3. stirringthe mixture stirred overnight
  4. stirringthe mixture stirred overnight when LCMS
  5. customreaction
  6. filtrationThe mixture was filtered
  7. washthe filtrate was washed with water
  8. extractionThe aqueous phase was back-extracted with dichloromethane
  9. customthe combined organic phases were dried
  10. customevaporated
  11. customto give crude product which
  12. customwas purified by silica gel chromatography
  13. washeluting with a 0 to 50% dichloromethane

出典と根拠

ORDレコード
ord-8ffb26c219254c14a3bd6cb2cf47a1ae
出典データセット
uspto-grants-2011_05
特許番号
US07947727B2

関連ノート

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