2,6-Dibromopyridine → 6-bromo-N-(3-fluorobenzyl)pyridin-2-amine
Reaction equation
Br[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Br:8])[N:3]=1.CN1C(=O)CCC1.[F:16][C:17]1[CH:18]=[C:19]([CH2:23][NH2:24])[CH:20]=[CH:21][CH:22]=1.CCN(C(C)C)C(C)C>C(OCC)(=O)C>[Br:8][C:4]1[N:3]=[C:2]([NH:24][CH2:23][C:19]2[CH:20]=[CH:21][CH:22]=[C:17]([F:16])[CH:18]=2)[CH:7]=[CH:6][CH:5]=1Participants
Conditions
- Temperature
- 117.5 °C
Procedure
To 2,6-dibromopyridine (7.1 g, 30.0 mmol) was added NMP (16 ml), (3-fluorophenyl)methanamine (4.13 g, 33.0 mmol) and Huenig's Base (5.76 ml, 33.0 mmol) flushed with argon. The crude reaction mixture was stirred at 115-120° C. for 168 hr, followed by LCMS. The crude mixture was cooled, 250 ml of ethyl acetate was added, washed with saturated sodium bicarbonate (2×), water (2×), saturated salt solution (1×), dried sodium sulfate, filtered, concentrate. The crude was purified by silica gel chromatography using 120 g column, eluting from 0%-20% ethyl acetate with hexane. The desired fractions were concentrated to constant mass, giving 7.11 grams of the titled compound as a free base used without further purification. LCMS (m/z): 281.1/283.1 (MH+), retention time=1.03 min.
Workup
- customflushed with argon
- customThe crude reaction mixture
- washwashed with saturated sodium bicarbonate (2×), water (2×), saturated salt solution (1×), dried sodium sulfate
- filtrationfiltered
- concentrationconcentrate
- customThe crude was purified by silica gel chromatography
- washeluting from 0%-20% ethyl acetate with hexane
- concentrationThe desired fractions were concentrated to constant mass
Sources & evidence
- ORD record
- ord-dbfbd9461e0a4ddda7f0550ceac5ceb7
- Source dataset
- uspto-grants-2014_07
- Patent number
- US08778951B2
Reaction notes
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