Acetonitrile → 9-fluoro-6-(1-methyl-2-morpholin-4-ylethyl)benzo[c]-1,6-naphthyridin-1(2H)-one
Reaction equation
Br[CH2:2][CH:3]([C:5]1[C:14]2[CH:15]=[CH:16][C:17]([F:19])=[CH:18][C:13]=2[C:12]2[C:11](=[O:20])[NH:10][CH:9]=[CH:8][C:7]=2[N:6]=1)[CH3:4].C(#N)C.[NH:24]1[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1>>[F:19][C:17]1[CH:16]=[CH:15][C:14]2[C:5]([CH:3]([CH3:4])[CH2:2][N:24]3[CH2:29][CH2:28][O:27][CH2:26][CH2:25]3)=[N:6][C:7]3[CH:8]=[CH:9][NH:10][C:11](=[O:20])[C:12]=3[C:13]=2[CH:18]=1Participants
Conditions
- Temperature
- 100 °C
Procedure
A suspension of 6-(2-bromo-1-methylethyl)-9-fluorobenzo[c]-1,6-naphthyridin-1(2H)-one (HBr salt) (25 mg, 0.060 mmol) in morpholine (1.0 mL) was stirred at 100° C. for 1 h. After cooling to room temperature, acetonitrile was added, and the resulting solution was concentrated to a crude residue. The resulting crude residue was purified by preparative reverse phase HPLC eluting with an acetonitrile/water (with 0.05% TFA as a modifier) gradient to afford 9-fluoro-6-(1-methyl-2-morpholin-4-ylethyl)benzo[c]-1,6-naphthyridin-1(2H)-one. 1H NMR (500 MHz, DMSO-D6). δ 11.86 (br d, 1H), 9.76 (dd, 1H), 8.63 (dd, 1H), 7.62 (br t, 1H), 7.57 (br t, 1H), 6.76 (d, 1H), 4.20 (br m, 1H), 3.47 (br s, 4H), 2.80 (br dd, 1H), 2.65 (br m, 1H), 2.43 (br s, 4H), 1.33 (d, 3H). LRMS (ESI) calc'd for (C19H20FN3O2) [M+H]+, 342.2; found 342.1.
Workup
- temperatureAfter cooling to room temperature
- concentrationthe resulting solution was concentrated to a crude residue
- customThe resulting crude residue was purified by preparative reverse phase HPLC
- washeluting with an acetonitrile/water (with 0.05% TFA as a modifier) gradient
Sources & evidence
- ORD record
- ord-d05c75a40bb14d0891d7e87ad04fb43a
- Source dataset
- uspto-grants-2012_12
- Patent number
- US08329722B2
Reaction notes
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