Cyclohexane → 6-methoxy-3-(4-nitro-pyrazol-1-ylmethyl)-3,4-dihydro-2H-1-oxa-9-aza-phenanthrene

HRID 633815Notes

Reaction equation

[N+:1]([C:4]1[CH:5]=[N:6][NH:7][CH:8]=1)([O-:3])=[O:2].Br[CH2:10][CH:11]1[CH2:24][C:23]2[C:22]3[C:17](=[CH:18][CH:19]=[C:20]([O:25][CH3:26])[CH:21]=3)[N:16]=[CH:15][C:14]=2[O:13][CH2:12]1.C(N(CC)C(C)C)(C)C.C1CCCCC1>CN(C)C=O.C(OCC)(=O)C>[CH3:26][O:25][C:20]1[CH:21]=[C:22]2[C:17](=[CH:18][CH:19]=1)[N:16]=[CH:15][C:14]1[O:13][CH2:12][CH:11]([CH2:10][N:6]3[CH:5]=[C:4]([N+:1]([O-:3])=[O:2])[CH:8]=[N:7]3)[CH2:24][C:23]2=1

Participants

Conditions

Temperature: 80 °C

Procedure

4-Nitro-1H-pyrazole (118 mg, 1.02 mmol, 1.0 eq) is added at room temperature to a stirred solution of 3-bromomethyl-6-methoxy-3,4-dihydro-2H-1-oxa-9-aza-phenanthrene (350 mg, 1.02 mmol, 1.0 eq) in N,N-dimethylformamide (12 mL), followed by N,N-diisopropylethylamine (196 μL, 1.12 mmol, 1.1 eq). After 24 hours stirring at 80° C., solvent is removed and the residue is extracted with dichloromethane (3×20 mL) and water (20 mL). The combined organic layers are dried over sodium sulfate, filtered and concentrated to give a residue that is purified by column chromatography (silica gel, eluent: cyclohexane:ethyl acetate, 1:1 to 0:1, v/v) to afford 6-methoxy-3-(4-nitro-pyrazol-1-ylmethyl)-3,4-dihydro-2H-1-oxa-9-aza-phenanthrene as a light yellow viscous oil (222 mg, 61% yield).

Workup

customsolvent is removed
extractionthe residue is extracted with dichloromethane (3×20 mL) and water (20 mL)
dry with materialThe combined organic layers are dried over sodium sulfate
filtrationfiltered
concentrationconcentrated
customto give a residue that
customis purified by column chromatography (silica gel, eluent

Sources & evidence

ORD record: ord-a55cb16889f84da69666cc3d72754bfa
Source dataset: uspto-grants-2016_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09321788B2

Reaction notes

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