2-Bromopropane → Methyl 6-bromo-2-(propan-2-yl)-2H-indazole-4-carboxylate

HRID 1476380

反応式

HRID 1476380 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+].Br[CH:18]([CH3:20])[CH3:19]>CN(C)C=O>[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]([CH3:20])[CH3:19])[C:9]=2[CH:10]=1.[Br:1][C:2]1[CH:3]=[C:4]([C:11]([O:13][CH3:14])=[O:12])[C:5]2[C:9]([CH:10]=1)=[N:8][N:7]([CH:18]([CH3:20])[CH3:19])[CH:6]=2

参加物

6

反応物 3

HCID 63582-BromopropaneHCID 24758Sodium hydrideHCID 24728062methyl 6-bromo-1H-indazole-4-carboxylate

生成物 2

HCID 67464993Methyl 6-bromo-1-isopropyl-1H-indazole-4-carboxylate収率 40%HCID 67465809Methyl 6-bromo-2-(propan-2-yl)-2H-indazole-4-carboxylate収率 43%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

To a cooled (0° C.) solution of methyl 6-bromo-1H-indazole-4-carboxylate (1.25 g, 4.90 mmol) in N,N-dimethylformamide (25 mL) was added sodium hydride (0.216 g, 5.39 mmol). The reaction mixture was stirred for 15 min, then 2-bromopropane (0.920 mL, 9.80 mmol) was added and the reaction allowed to warm to RT. The reaction was maintained at RT overnight. The contents were concentrated to about ½ volume, then poured into saturated NH4Cl (200 mL) with stirring. The contents were extracted with ether (2×) and the combined organics washed with brine, dried (MgSO4), filtered, and concentrated to give an orange residue (1.55 g crude). Purification by silica gel chromatography (eluent: 5-25% ethyl acetate in hexanes) gave methyl 6-bromo-1-(1-methylethyl)-1H-indazole-4-carboxylate (0.60 g, 40% yield) and methyl 6-bromo-2-(1-methylethyl)-2H-indazole-4-carboxylate (0.65 g, 43% yield). Both products were isolated and methyl 6-bromo-1-(1-methylethyl)-1H-indazole-4-carboxylate was taken on to the next step. Data for 1-alkylated isomer: 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 8.48 (s, 1H) 8.02 (d, J=1.52 Hz, 1H) 7.85 (s, 1H) 4.83 (dt, J=13.33, 6.60 Hz, 1H) 4.04 (s, 3H) 1.63 (s, 3H) 1.61 (s, 3H); LC-MS (ES) [M+H]+ 297.5/299.5. Data for 2-alkylated isomer: 1H NMR (400 MHz, DMSO-d6) δ ppm 8.72 (s, 1H), 8.25 (s, 1H), 7.80 (d, J=1.5 Hz, 1H), 4.96 (m, 1H), 3.95 (s, 3H), 1.57 (d, J=6.6 Hz, 6H); LC-MS (ES) [M+H]+ 297.5/299.5.

後処理

  1. temperatureThe reaction was maintained at RT overnight
  2. concentrationThe contents were concentrated to about ½ volume
  3. additionpoured into saturated NH4Cl (200 mL)
  4. stirringwith stirring
  5. extractionThe contents were extracted with ether (2×)
  6. washthe combined organics washed with brine
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customto give an orange residue (1.55 g crude)
  11. customPurification by silica gel chromatography (eluent: 5-25% ethyl acetate in hexanes)

出典と根拠

ORDレコード
ord-0767635cba084e9a9d3efabe5c16beba
出典データセット
uspto-grants-2015_04
特許番号
US09018382B2

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