Nitrogen → 5-Methoxy-1-methylindazole

HRID 1715583

Reaction equation

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

Participants

Conditions

Temperature: 110 °C

Procedure

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.

Workup

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

Sources & evidence

ORD record: ord-f8d0bad32dfe4952b681849684c301d6
Source dataset: uspto-grants-2010_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07799782B2

Linked notes

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