Potassium Carbonate → 2-methoxy-5-((2-(1-methyl-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)isonicotinaldehyde

HRID 1471693Notes

Reaction equation

[OH:1][C:2]1[C:7]([CH:8]=[O:9])=[CH:6][C:5]([O:10][CH3:11])=[N:4][CH:3]=1.Cl.Cl[CH2:14][C:15]1[C:16]([C:21]2[N:25]([CH3:26])[N:24]=[CH:23][CH:22]=2)=[N:17][CH:18]=[CH:19][CH:20]=1.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[CH3:11][O:10][C:5]1[CH:6]=[C:7]([C:2]([O:1][CH2:14][C:15]2[C:16]([C:21]3[N:25]([CH3:26])[N:24]=[CH:23][CH:22]=3)=[N:17][CH:18]=[CH:19][CH:20]=2)=[CH:3][N:4]=1)[CH:8]=[O:9]

Participants

Conditions

Temperature: 70 °C

Procedure

A mixture of 5-hydroxy-2-methoxyisonicotinaldehyde (147 mg, 0.96 mmol, 1 eq.), 3-(chloromethyl)-2-(1-methyl-1H-pyrazol-5-yl)pyridine hydrochloride (236 mg, 0.96 mmol, 1 eq.), and K2CO3 (532 mg, 3.85 mmol, 3 eq.) in DMF (3.0 mL) was heated at 70° C. for 2 h. The mixture was cooled, filtered, concentrated, and purified on silica gel using a mixture of EtOAc and hexanes as eluent to give 2-methoxy-5-((2-(1-methyl-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)isonicotinaldehyde (232.5 mg, 75%) as an off-white solid. 1H NMR (400 MHz, CDCl3) δ 10.40 (s, 1H), 8.77 (dd, J=4.7, 1.7 Hz, 1H), 8.03 (dd, J=7.9, 1.7 Hz, 1H), 7.93 (s, 1H), 7.55 (d, J=1.9 Hz, 1H), 7.44 (dd, J=7.9, 4.8 Hz, 1H), 7.11 (d, J=0.4 Hz, 1H), 6.43 (d, J=1.9 Hz, 1H), 5.20 (s, 2H), 3.97 (s, 3H), 3.92 (s, 3H). LRMS (M+H+) m/z 325.1.

Workup

temperatureThe mixture was cooled
filtrationfiltered
concentrationconcentrated
custompurified on silica gel using
additiona mixture of EtOAc and hexanes as eluent

Sources & evidence

ORD record: ord-240db8d27cbd4b2199fc2ae7c6b6dec6
Source dataset: uspto-grants-2015_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09012450B2

Reaction notes

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