Nitrogen → 5-Methoxy-1-methylindazole

HRID 909162

반응식

HRID 909162 반응식
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

참가 물질

6

반응물 4

HCID 947NitrogenHCID 6328Methyl iodide2회HCID 11430Potassium CarbonateHCID 126392026-Methoxy-1H-indazole

생성물 1

HCID 574187495-Methoxy-1-methylindazole수율 47%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

반응 조건

온도
110 °C

실험 절차

A solution of 6-methoxy indazole (it) (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.

후처리

  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

출처 및 근거

ORD 기록
ord-6a0d52543d8843bb9b9377f6aa7824f0
출처 데이터셋
uspto-grants-2011_09
특허 번호
US08017641B2

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