Methyl iodide → HCID 66793360, compound

HRID 2069567Notes

Reaction equation

[H-].[Na+].[O:3]1[CH2:8][CH2:7][CH2:6][CH2:5][CH:4]1[N:9]1[C:17]2[C:12](=[CH:13][C:14]([C:18]#[C:19][CH2:20][OH:21])=[CH:15][CH:16]=2)[CH:11]=[N:10]1.I[CH3:23]>C1COCC1>[CH3:23][O:21][CH2:20][C:19]#[C:18][C:14]1[CH:13]=[C:12]2[C:17](=[CH:16][CH:15]=1)[N:9]([CH:4]1[CH2:5][CH2:6][CH2:7][CH2:8][O:3]1)[N:10]=[CH:11]2

Participants

Conditions

Temperature: 0 °C

Procedure

Sodium hydride (60% in mineral oil, 0.42 g, 10.5 mmol) was added to a solution of 3-(1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-5-yl)prop-2-yn-1-ol (1.01 g, 3.94 mmol; Intermediate 16) in THF (20 mL) at 0° C. The mixture was stirred at 0° C. for 30 minutes, and then iodomethane (1.67 g, 11.8 mmol) was added. The resulting mixture was stirred at room temperature for 16 h. The reaction mixture was poured into ice water (100 mL) and extracted with EtOAc (3×100 mL). The combined organic layers were washed with brine (100 mL), dried over anhydrous sodium sulfate, and concentrated in vacuo. The residue was purified by column chromatography on silica gel (EtOAc/petroleum ether=1:30) to afford the title compound (0.714 g, yield 67.3%). 1H NMR (DMSO-d6, 300 MHz): δ 8.21 (s, 1H), 7.93 (s, 1H), 7.73 (d, 1H), 7.47-7.45 (m, 1H), 5.85-5.83 (m, 1H), 4.38 (s, 2H), 3.76-3.71 (m, 2H), 3.35 (s, 3H), 2.40-2.37 (m, 1H), 2.03-1.94 (m, 2H), 1.73-1.72 (m, 1H), 1.57-1.55 (m, 2H). LCMS: 271 (M+H)+.

Workup

stirringThe resulting mixture was stirred at room temperature for 16 h
extractionextracted with EtOAc (3×100 mL)
washThe combined organic layers were washed with brine (100 mL)
dry with materialdried over anhydrous sodium sulfate
concentrationconcentrated in vacuo
customThe residue was purified by column chromatography on silica gel (EtOAc/petroleum ether=1:30)

Sources & evidence

ORD record: ord-4b0e4f72703c4c3ba90d836bece112a3
Source dataset: uspto-grants-2012_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08299112B2

Reaction notes

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