Cesium carbonate → 2-(2-methoxyethoxy)-5-((2-(1-methyl-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)isonicotinaldehyde

HRID 1471728Notes

Reaction equation

[OH:1][C:2]1[C:7]([CH:8]=[O:9])=[CH:6][C:5]([O:10][CH2:11][CH2:12][O:13][CH3:14])=[N:4][CH:3]=1.Cl.Cl[CH2:17][C:18]1[C:19]([C:24]2[N:28]([CH3:29])[N:27]=[CH:26][CH:25]=2)=[N:20][CH:21]=[CH:22][CH:23]=1.C([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C>[CH3:14][O:13][CH2:12][CH2:11][O:10][C:5]1[CH:6]=[C:7]([C:2]([O:1][CH2:17][C:18]2[C:19]([C:24]3[N:28]([CH3:29])[N:27]=[CH:26][CH:25]=3)=[N:20][CH:21]=[CH:22][CH:23]=2)=[CH:3][N:4]=1)[CH:8]=[O:9]

Participants

Conditions

Temperature: 60 °C

Procedure

A mixture of 5-hydroxy-2-(2-methoxyethoxy)isonicotinaldehyde (125 mg, 0.63 mmol, 1 eq.), 3-(chloromethyl)-2-(1-methyl-1H-pyrazol-5-yl)pyridine hydrochloride salt (120 mg, 0.63 mmol, 1 eq.), and Cs2CO3 (410 mg, 1.26 mmol, 2 eq.) in DMF (3.0 mL) was heated at 60° 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-(2-methoxyethoxy)-5-((2-(1-methyl-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)isonicotinaldehyde (59 mg, 25%) as a yellow oil. 1H NMR (400 MHz, CDCl3) δ 10.22 (s, 1H), 8.59 (dd, J=4.7, 1.6 Hz, 1H), 7.87 (dd, J=7.9, 1.3 Hz, 1H), 7.73 (s, 1H), 7.38 (d, J=1.9 Hz, 1H), 7.27 (dd, J=7.9, 4.8 Hz, 1H), 7.00 (s, 1H), 6.25 (d, J=1.9 Hz, 1H), 5.02 (s, 2H), 4.26 (dd, J=5.4, 3.9 Hz, 2H), 3.80 (s, 3H), 3.57 (dd, J=5.4, 3.9 Hz, 2H), 3.28 (s, 3H). LRMS (M+H+) m/z 387.1.

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-43dc705d84ef4cba8eaa4fa70128e499
Source dataset: uspto-grants-2015_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09012450B2

Reaction notes

Loading…