Potassium Carbonate → methyl 3-(3-(3-((4-formyl-6-methoxypyridin-3-yloxy)methyl)pyridin-2-yl)-1H-pyrazol-1-yl)propanoate

HRID 1471759Notes

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[CH:25]=[CH:24][N:23]([CH2:26][CH2:27][C:28]([O:30][CH3:31])=[O:29])[N:22]=2)=[N:17][CH:18]=[CH:19][CH:20]=1.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[CH:8]([C:7]1[CH:6]=[C:5]([O:10][CH3:11])[N:4]=[CH:3][C:2]=1[O:1][CH2:14][C:15]1[C:16]([C:21]2[CH:25]=[CH:24][N:23]([CH2:26][CH2:27][C:28]([O:30][CH3:31])=[O:29])[N:22]=2)=[N:17][CH:18]=[CH:19][CH:20]=1)=[O:9]

Participants

Conditions

Temperature: 70 °C

Procedure

A mixture of 5-hydroxy-2-methoxyisonicotinaldehyde (30 mg, 0.20 mmol, 1 eq.), methyl 3-(3-(3-(chloromethyl)pyridin-2-yl)-1H-pyrazol-1-yl)propanoate hydrochloride (63 mg, 0.20 mmol, 1 eq.), and K2CO3 (100 mg, 10.32 mmol, 4 eq.) in DMF (5.0 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 methyl 3-(3-(3-((4-formyl-6-methoxypyridin-3-yloxy)methyl)pyridin-2-yl)-1H-pyrazol-1-yl)propanoate (88 mg, quantitative yield) as a white solid. 1H NMR (400 MHz, CDCl3) δ 10.50 (s, 1H), 8.65 (dd, J=4.7, 0.9 Hz, 1H), 8.09 (s, 1H), 8.02 (dd, J=7.8, 0.8 Hz, 1H), 7.53 (d, J=2.3 Hz, 1H), 7.31 (dd, J=7.9, 4.8 Hz, 1H), 7.12 (s, 1H), 6.96 (d, J=2.3 Hz, 1H), 5.71 (s, 2H), 4.46 (t, J=6.6 Hz, 2H), 3.93 (s, 3H), 3.69 (s, 3H), 2.91 (t, J=6.6 Hz, 2H). LRMS (M+H+) m/z 397.1.

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-75233c22f0004a6ea14a207f03f587ba
Source dataset: uspto-grants-2015_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09012450B2

Reaction notes

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