Methyl iodide → Methyl 6-chloro-1-(1-methylethyl)-1H-indazole-4-carboxylate

HRID 85410ノート

反応式

HRID 85410 の反応式
[Cl:1][C:2]1[CH:3]=[C:4]([C:11]([O:13][CH3:14])=[O:12])[C:5]2[CH:6]=[N:7][NH:8][C:9]=2[CH:10]=1.[H-].[Na+].I[CH:18]([CH3:20])[CH3:19].C(=O)([O-])[O-].[Na+].[Na+].CI>CN(C=O)C.[NH4+].[Cl-]>[Cl:1][C:2]1[CH:3]=[C:4]([C:11]([O:13][CH3:14])=[O:12])[C:5]2[CH:6]=[N:7][N:8]([CH:18]([CH3:20])[CH3:19])[C:9]=2[CH:10]=1

参加物

8

反応物 5

HCID 6328Methyl iodideHCID 6362Isopropyl iodideHCID 10340Sodium CarbonateHCID 24758Sodium hydrideHCID 24728139Methyl 6-chloro-1H-indazole-4-carboxylate

生成物 1

HCID 67468514Methyl 6-chloro-1-(1-methylethyl)-1H-indazole-4-carboxylate収率 45%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 25517Ammonium Chloride溶媒

実験手順

Methyl 6-chloro-1H-indazole-4-carboxylate (0.410 g, 1.947 mmol) was dissolved in DMF (10 mL) and placed into an ice bath and stirred for 15 min. Sodium hydride (0.101 g, 2.53 mmol) was added, the contents stirred for 15 min., and then 2-iodopropane (0.389 mL, 3.89 mmol) was added. The contents were stirred with warming to RT. After stirring at RT for 2 h, a scoop of sodium carbonate and then 0.4 mL of methyl iodide were added. After stirring at RT for an additional 1 h, the reaction mixture was diluted with saturated NH4Cl and then extracted with EtOAc (2×). The combined organic layers were washed with brine, dried over MgSO4, filtered, and concentrated in vacuo. The crude residue was dissolved in a minimal amount of DCM and purified by silica gel chromatography (eluent: 3-20% ethyl acetate in hexanes). The title compound was the less polar of the two products separated from chromatography, and was collected as 0.22 g (45% yield). 1H NMR (400 MHz, DMSO-d6) ppm 1.45-1.52 (m, 6H), 3.93-3.99 (m, 3H), 5.11 (quin, J=6.57 Hz, 1H), 7.73 (d, J=1.77 Hz, 1H), 8.30 (s, 1H), 8.42 (s, 1H).

後処理

  1. customplaced into an ice bath
  2. stirringthe contents stirred for 15 min.
  3. stirringThe contents were stirred
  4. stirringAfter stirring at RT for 2 h
  5. stirringAfter stirring at RT for an additional 1 h
  6. extractionextracted with EtOAc (2×)
  7. washThe combined organic layers were washed with brine
  8. dry with materialdried over MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. dissolutionThe crude residue was dissolved in a minimal amount of DCM
  12. custompurified by silica gel chromatography (eluent: 3-20% ethyl acetate in hexanes)
  13. customseparated from chromatography
  14. customwas collected as 0.22 g (45% yield)

出典と根拠

ORDレコード
ord-7376f010bd754760b4b8c589cc096599
出典データセット
uspto-grants-2014_09
特許番号
US08846935B2

反応ノート

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