3-Pyridinemethanol → HCID 67006925, compound
Reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([CH2:7][OH:8])[CH:2]=1.C1N=CN([C:14](N2C=NC=C2)=[O:15])C=1.C1CCN2C(=NCCC2)CC1.[C@H:32]12[CH2:38][C@H:35]([NH:36][CH2:37]1)[CH2:34][N:33]2[C:39]1[N:44]=[CH:43][C:42]([C:45]([O:47][CH2:48][CH3:49])=[O:46])=[CH:41][N:40]=1>C1COCC1.C(OCC)(=O)C>[CH2:48]([O:47][C:45]([C:42]1[CH:41]=[N:40][C:39]([N:33]2[CH2:34][C@@H:35]3[CH2:38][C@H:32]2[CH2:37][N:36]3[C:14]([O:8][CH2:7][C:3]2[CH:2]=[N:1][CH:6]=[CH:5][CH:4]=2)=[O:15])=[N:44][CH:43]=1)=[O:46])[CH3:49]Participants
Conditions
- Temperature
- 45 °C
Procedure
To a solution of pyridin-3-ylmethanol (0.086 mL, 0.878 mmol) in THF (2.5 mL) was added N,N-carbonyldiimidazole (0.142 g, 0.878 mmol). After stirring for 1 h a solution of TEA (0.245 mL, 1.756 mmol), DBU (0.132 mL, 0.878 mmol) and the title compound 212 (0.25 g, 0.878 mmol) in THF (2.5 mL) was added. The reaction mixture was stirred overnight at 45° C. The mixture was cooled down and diluted with ethyl acetate. The organic layer was washed with water, brine, dried over Na2SO4, filtered and concentrated. The crude was purified by flash chromatography (twice): 40 SiO2, MeOH/EA 0% to 20% over 20 min to afford title compound 221 (80 mg, 24%) as an oil. 1H NMR (400 MHz, CDCl3) δ (ppm): 8.81-8.77 (m, 2H), 8.60-8.57 (m, 2H), 7.83-7.76 (m, 1H), 7.42-7.35 (m, 1H), 5.21-5.05 (m, 1H), 5.21 (s, 2H), 4.79 (s, 1H), 4.72-4.64 (m, 1H), 4.31 (qd, J=7.1, 1.8 Hz, 2H), 3.69-3.41 (m, 3H), 1.98 (d, J=8.0 Hz, 2H), 1.34 (td, J=7.1, 2.5 Hz, 3H).
Workup
- temperatureThe mixture was cooled down
- washThe organic layer was washed with water, brine
- dry with materialdried over Na2SO4
- filtrationfiltered
- concentrationconcentrated
- customThe crude was purified by flash chromatography (twice): 40 SiO2, MeOH/EA 0% to 20% over 20 min
Sources & evidence
- ORD record
- ord-1b4e62c9884e4e6686690de517fd9895
- Source dataset
- uspto-grants-2013_03
- Patent number
- US08399452B2
Reaction notes
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