Hydrochloric Acid → 5-((2-(4-methyl-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)-2-oxo-1,2-dihydropyridine-4-carbaldehyde
Reaction equation
C[O:2][C:3]1[CH:4]=[C:5]([C:8]([O:11][CH2:12][C:13]2[C:14]([C:19]3[NH:23][N:22]=[CH:21][C:20]=3[CH3:24])=[N:15][CH:16]=[CH:17][CH:18]=2)=[CH:9][N:10]=1)[CH:6]=[O:7].Cl.[OH-].[Na+]>O>[CH3:24][C:20]1[CH:21]=[N:22][NH:23][C:19]=1[C:14]1[C:13]([CH2:12][O:11][C:8]2[C:5]([CH:6]=[O:7])=[CH:4][C:3](=[O:2])[NH:10][CH:9]=2)=[CH:18][CH:17]=[CH:16][N:15]=1Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Procedure
To 2-methoxy-5-((2-(4-methyl-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)isonicotinaldehyde (862 mg, 2.66 mmol, 1 equiv) suspended in water (5.0 mL) was added HCl (6 N, 4.43 mL, 26.6 mmol, 10 eq.). Once the mixture turned into a homogeneous solution, it was freeze at −78° C. to an solid and pump under high vacuum O/N. The yellow solid was continued to pump at 45° C. for 20 h, dissolved in water (2.0 mL), and basified to pH 11 with NaOH (2 N). The aqueous layer was washed with DCM three times and the pH of the mixture was adjusted to pH 6-7. The solid was collected and dried to give 5-((2-(4-methyl-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)-2-oxo-1,2-dihydropyridine-4-carbaldehyde (180 mg, 44% based on 50% recovered of SM) as a white solid. 1H NMR (400 MHz, DMSO at 90° C.) δ 10.14 (s, 1H), 8.63 (s, 1H), 8.09-8.03 (br, 1H), 7.56-7.50 (br, 2H), 7.42-7.35 (br, 1H), 6.70 (s, 1H), 5.39 (s, 2H), 2.18 (s, 3H). LRMS (M+H+) m/z 311.1.
Workup
- customat −78° C.
- washThe aqueous layer was washed with DCM three times
- customThe solid was collected
- customdried
Sources & evidence
- ORD record
- ord-5c83954b8fbf4a58bf9daeb17e502c42
- Source dataset
- uspto-grants-2015_04
- Patent number
- US09012450B2
Reaction notes
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