Nitrogen → 5-Methoxy-1-methylindazole

HRID 1897442

反応式

HRID 1897442 の反応式
CO[C:3]1[CH:11]=[C:10]2[C:6]([CH:7]=[N:8][NH:9]2)=[CH:5][CH:4]=1.[C:12](=[O:15])([O-])[O-].[K+].[K+].[CH3:18]I.N#N>CN(C=O)C>[CH3:12][O:15][C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:3]=1)[N:9]([CH3:18])[N:8]=[CH:7]2

参加物

6

反応物 4

HCID 947NitrogenHCID 6328Methyl iodide2 回HCID 11430Potassium CarbonateHCID 126392026-Methoxy-1H-indazole

生成物 1

HCID 574187495-Methoxy-1-methylindazole収率 47%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
110 °C

実験手順

A solution of 6-methoxy indazole (1t) (5 g, 33.75 mmol; see Tet Lett., 43(15): 2695 (2002)) in DMF (200 mL) was treated with potassium carbonate (6.06 g, 43.87 mmol) at room temperature. After stirring at for 15 minutes, methyl iodide (2.33 mL, 37.12 mmol) was added. The resulting mixture was heated at 110° C. for 18 hours. LC showed minor starting material left. Additional methyl iodide was added (2.33 mL) and stirring continued for an additional 18 hours. LC showed a 2:1 mixture of the N1 to N2 alkylated isomers. The solvent was evaporated in vacuo and the residue taken up in DCM and washed with 1N HCl. The organic layer was filtered through 1 PS paper, evaporated in vacuo and purified on the Biotage eluting with 4:3, 3:1 hexane/Et2O. The desired combined fractions (N1 isomer) were evaporated in vacuo to provide the desired product (2t) as a yellow oil (2.57 g; 47%). 1H NMR (400 MHz, CDCl3) δ 7.38 (d, J=7.8 Hz, 1H), 7.17 (dd, J=7.8, 1.6 Hz, 1H), 7.13 (d, J=1.6 Hz, 1H), 5.19-5.18 (m, 1H), 4.51-4.44 (m, 1H), 4.43-4.36 (m, 1H), 2.53-2.45 (m, 1H), 2.36-2.30 (m, 1H); MS (ESI+) m/z 163 (M+H) detected.

後処理

  1. additionwas added
  2. waitleft
  3. customThe solvent was evaporated in vacuo
  4. washwashed with 1N HCl
  5. filtrationThe organic layer was filtered through 1 PS paper
  6. customevaporated in vacuo
  7. custompurified on the Biotage
  8. washeluting with 4:3, 3:1 hexane/Et2O
  9. customwere evaporated in vacuo

出典と根拠

ORDレコード
ord-935e702571b64a46affe0c51515bcce4
出典データセット
uspto-grants-2013_08
特許番号
US08518983B2

関連ノート

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