Sodium hydride → Methyl 6-bromo-1-cyclopentyl-1H-indazole-4-carboxylate

HRID 85459

反応式

HRID 85459 の反応式
[Br: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]1[CH2:22][CH2:21][CH2:20][CH2:19]1>CN(C=O)C>[Br: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]3[CH2:22][CH2:21][CH2:20][CH2:19]3)[C:9]=2[CH:10]=1

参加物

5

反応物 3

HCID 24758Sodium hydrideHCID 73784IodocyclopentaneHCID 24728062methyl 6-bromo-1H-indazole-4-carboxylate

生成物 1

HCID 67468180Methyl 6-bromo-1-cyclopentyl-1H-indazole-4-carboxylate

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
0 °C

実験手順

Ice-cooled methyl 6-bromo-1H-indazole-4-carboxylate (2 g, 7.84 mmol) in 30 mL of DMF was treated with NaH (60%, 345 mg, 8.63 mmol) and the mixture was stirred for 1 hr at 0° C. Iodocyclopentane (2.31 g, 11.8 mmol) was then added and the mixture was stirred at 100° C. overnight. After cooling to RT, the reaction mixture was partitioned between water and ethyl acetate. The organic phase was washed with water and brine, dried over MgSO4, filtered and evaporated. Hexanes was added to the brown oil and it was purified using silica gel chromatography (eluent: Hex/EtOAc, gradient 0 to 25%). The less polar product was evaporated to give an orange oil, and was dried on hivac overnight. The product was confirmed to be the alkylated 1-isomer as suggested by 2D HNMR, and was collected as 807 mg (32%). 1H NMR (400 MHz, DMSO-d6): δ 8.40 (s, 1H) 8.37 (s, 1H) 7.81 (d, J=1.52 Hz, 1H) 5.26 (quin, J=7.07 Hz, 1H) 3.95 (s, 3H) 2.08-2.17 (m, 2H) 1.93-2.01 (m, 2H) 1.82-1.92 (m, 2H) 1.64-1.73 (m, 2H); LCMS (ES+): m/z=323.3/325.3

後処理

  1. stirringthe mixture was stirred at 100° C. overnight
  2. temperatureAfter cooling to RT
  3. customthe reaction mixture was partitioned between water and ethyl acetate
  4. washThe organic phase was washed with water and brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. customevaporated
  8. additionHexanes was added to the brown oil and it
  9. customwas purified
  10. customThe less polar product was evaporated
  11. customto give an orange oil
  12. customwas dried on hivac overnight
  13. customwas collected as 807 mg (32%)

出典と根拠

ORDレコード
ord-7d877e0a470e43e2ad35bc176c4be984
出典データセット
uspto-grants-2014_09
特許番号
US08846935B2

関連ノート

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