Methyl iodide → 5-Fluoro-2-(1-methyl-1H-pyrazolo[3,4-c]pyridin-5-yloxy)-benzonitrile

HRID 2112166Notes

Reaction equation

[F:1][C:2]1[CH:3]=[CH:4][C:5]([O:10][C:11]2[CH:12]=[C:13]3[CH:19]=[N:18][NH:17][C:14]3=[CH:15][N:16]=2)=[C:6]([CH:9]=1)[C:7]#[N:8].[H-].[Na+].[CH3:22]I>CN(C=O)C>[F:1][C:2]1[CH:3]=[CH:4][C:5]([O:10][C:11]2[CH:12]=[C:13]3[CH:19]=[N:18][N:17]([CH3:22])[C:14]3=[CH:15][N:16]=2)=[C:6]([CH:9]=1)[C:7]#[N:8]

Participants

Conditions

Temperature: 0 °C

Procedure

The intermediate (2u) (0.23 g) was dissolved in DMF (9 mL) and cooled to 0° C. Sodium hydride (60% in oil, 0.054 g, 1.36 mmol) and methyl iodide (0.28 mL, 642 mg, 4.52 mmol) were added to the solution at 0° C. and then the reaction mixture was stirred for an hour at 0° C. The mixture was quenched with 10 mL of water and extracted three times with 30 mL of ether. The combined organic layer was washed with 5 mL of water twice and brine once, dried over MgSO4, filtered, and concentrated under reduced pressure. The crude oil residue was purified on silica gel with EtOAc/hexane (1:1) to afford colorless oil (3u) (0.124 g, 51% yield). 1HNMR (400 MHz, CDCl3) δ 8.56 (s, 1H), 8.02 (s, 1H), 7.40-7.32 (m, 2H), 7.31-7.23 (m, 2H), 7.11-7.05 (m, 1H, 4.17 (s, 3H) ppm.

Workup

customThe mixture was quenched with 10 mL of water
extractionextracted three times with 30 mL of ether
washThe combined organic layer was washed with 5 mL of water twice
dry with materialbrine once, dried over MgSO4
filtrationfiltered
concentrationconcentrated under reduced pressure
customThe crude oil residue was purified on silica gel with EtOAc/hexane (1:1)

Sources & evidence

ORD record: ord-37cd7afacccc493c90f41535c46656ce
Source dataset: uspto-grants-2009_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07521447B2

Reaction notes

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