Dimethylformamide → 3-[5-(7-azabicyclo[2.2.1]heptan-7-yl)-2-nitro-phenyl]-N,N-dimethyl-prop-2-yn-1-amine

HRID 1465136Notes

Reaction equation

Br[C:2]1[CH:3]=[C:4]([N:11]2[CH:15]3[CH2:16][CH2:17][CH:12]2[CH2:13][CH2:14]3)[CH:5]=[CH:6][C:7]=1[N+:8]([O-:10])=[O:9].CN(C=O)C.C(N(CC)CC)C.[CH3:30][N:31]([CH3:35])[CH2:32][C:33]#[CH:34]>C(OCC)(=O)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I>[CH:15]12[N:11]([C:4]3[CH:5]=[CH:6][C:7]([N+:8]([O-:10])=[O:9])=[C:2]([C:34]#[C:33][CH2:32][N:31]([CH3:35])[CH3:30])[CH:3]=3)[CH:12]([CH2:17][CH2:16]1)[CH2:13][CH2:14]2

Participants

Conditions

Temperature: 100 °C

Procedure

To 7-(3-bromo-4-nitro-phenyl)-7-azabicyclo[2.2.1]heptane (500 mg, 1.68 mmol), Pd(PPh3)2Cl2 (59 mg, 0.08 mmol), and CuI (10 mg, 0.05 mmol) were added DMF (5 mL), triethylamine (5 mL), and N,N-dimethylprop-2-yn-1-amine (420 mg, 538 μL, 5.05 mmol) under N2 atmosphere. The reaction was heated under microwave irradiation for 10 min at 100° C. The reaction mixture was diluted with ethyl acetate, washed with 50% saturated NaHCO3 (2×20 mL), water, and brine. The organic layer was dried over Na2SO4, filtered, and concentrated in vacuo to a red solid. Purification by silica gel chromatography (0-50% dichloromethane/ethyl acetate) provided 3-[5-(7-Azabicyclo[2.2.1]heptan-7-yl)-2-nitro-phenyl]-N,N-dimethyl-prop-2-yn-1-amine (400 mg, 79% yield). LC/MS m/z 300.5 [M+H]+.

Workup

washwashed with 50% saturated NaHCO3 (2×20 mL), water, and brine
dry with materialThe organic layer was dried over Na2SO4
filtrationfiltered
concentrationconcentrated in vacuo to a red solid
customPurification by silica gel chromatography (0-50% dichloromethane/ethyl acetate)

Sources & evidence

ORD record: ord-a69204c25a974c8dad6ddc09416a073a
Source dataset: uspto-grants-2015_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08999976B2

Reaction notes

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