Water → 3-(5-(difluoromethoxy)-3-iodo-1H-indazol-1-yl)-N,N-dimethylpropan-1-amine

HRID 246700

Reaction equation

[F:1][CH:2]([F:14])[O:3][C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[NH:9][N:8]=[C:7]2[I:13].C([O-])([O-])=O.[K+].[K+].Cl[CH2:22][CH2:23][CH2:24][N:25]([CH3:27])[CH3:26].O>CN(C=O)C>[F:14][CH:2]([F:1])[O:3][C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[N:9]([CH2:22][CH2:23][CH2:24][N:25]([CH3:27])[CH3:26])[N:8]=[C:7]2[I:13]

Participants

Conditions

Temperature: 80 °C

Procedure

To a solution of 5-(difluoromethoxy)-3-iodo-1H-indazole (1 g, 3.2 mmol) in DMF (25 mL) was added K2CO3 (1.8 g, 12.8 mmol) and 3-chloro-N,N-dimethylpropan-1-amine (1.1 g, 6.4 mmol), after the addition, the reaction mixture was stirred at 80° C. for 4 hour. After cooling to room temperature, H2O (25 mL) was added and product extracted with ethyl acetate (100 mL). The organic layer was washed with H2O (100 mL), brine (100 mL), dried over Na2SO4 and concentrated under reduced pressure, the residue was purified by column chromatography (silica gel, 200-300 mesh, eluting with dichloromethane/CH3OH=10:1) to give 3-(5-(difluoromethoxy)-3-iodo-1H-indazol-1-yl)-N,N-dimethylpropan-1-amine (1.1 g, 78.5%) as yellow oil. 1H NMR (300 MHz, CDCl3): δ 7.46-7.42 (m, 1H), 7.27-7.17 (m, 2H), 6.87-6.29 (t, 1H, J=73.8 Hz), 4.47-4.41 (m, 2H), 2.24-2.18 (m, 8H), 2.08-2.03 (m, 2H). LCMS: (M+H)+=396.

Workup

additionafter the addition
temperatureAfter cooling to room temperature
extractionproduct extracted with ethyl acetate (100 mL)
washThe organic layer was washed with H2O (100 mL), brine (100 mL)
dry with materialdried over Na2SO4
concentrationconcentrated under reduced pressure
customthe residue was purified by column chromatography (silica gel, 200-300 mesh, eluting with dichloromethane/CH3OH=10:1)

Sources & evidence

ORD record: ord-e04eea713074407a9aa54e2b01a1b2be
Source dataset: uspto-grants-2014_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08658646B2

Linked notes

Loading…