Potassium Carbonate → 2-methoxy-6-((2-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)benzaldehyde

HRID 1484798Notes

Reaction equation

[OH:1][C:2]1[CH:9]=N[CH:7]=[C:6]([O:10][CH3:11])[C:3]=1[CH:4]=[O:5].Cl[CH2:13][C:14]1[C:15]([C:20]2[N:24]([CH2:25][C:26]([F:29])([F:28])[F:27])[N:23]=[CH:22][CH:21]=2)=[N:16][CH:17]=[CH:18][CH:19]=1.[C:30](=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[CH3:11][O:10][C:6]1[CH:7]=[CH:30][CH:9]=[C:2]([O:1][CH2:13][C:14]2[C:15]([C:20]3[N:24]([CH2:25][C:26]([F:29])([F:28])[F:27])[N:23]=[CH:22][CH:21]=3)=[N:16][CH:17]=[CH:18][CH:19]=2)[C:3]=1[CH:4]=[O:5]

Participants

Conditions

Temperature: 60 °C

Procedure

To a solution of 3-hydroxy-5-methoxyisonicotinaldehyde (0.13 g, 0.88 mmol) in DMF was added 3-(chloromethyl)-2-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-5-yl)pyridine (0.24 g, 0.88 mmol) (INT-2) and potassium carbonate (0.49 g, 3.52 mmol) and the reaction mixture was heated (60° C.). After 3 hours, the reaction mixture was filtered through a plug of silica (MeOH/CH2Cl2, 0-20%). Purification of the resulting residue by Prep-HPLC, provided 2-methoxy-6-((2-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)benzaldehyde (12 mg, 5% yield). NMR (400 MHz, Chloroform-d) δ 10.54 (s, 1H), 8.71 (dd, J=5.0, 1.8 Hz, 1H), 8.23 (s, 1H), 8.21 (ddd, J=7.9, 1.7, 0.7 Hz, 1H), 8.10 (s, 1H), 7.67 (dd, J=1.9, 0.5 Hz, 1H), 7.46 (dd, J=8.0, 4.5 Hz, 1H), 7.26 (d, J=0.5 Hz, 3H), 6.56 (dd, J=1.9, 0.5 Hz, 1H), 5.23 (s, 2H), 5.28-5.15 (m, 2H), 4.04 (s, 3H); MS (ESI) m/z 393 [M+Hr.

Workup

filtrationthe reaction mixture was filtered through a plug of silica (MeOH/CH2Cl2, 0-20%)
customPurification of the resulting residue by Prep-HPLC

Sources & evidence

ORD record: ord-5ab7422d644149c49fc867be8625dea2
Source dataset: uspto-grants-2016_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09422279B2

Reaction notes

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