Cesium carbonate → 4-(hydroxymethyl)-5-((2-(1-isopropyl-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)pyridin-3-ol
Reaction equation
[Si]([O:8][CH2:9][C:10]1[C:15]([OH:16])=[CH:14][N:13]=[CH:12][C:11]=1[OH:17])(C(C)(C)C)(C)C.C([O-])([O-])=O.[Cs+].[Cs+].Cl.Cl[CH2:26][C:27]1[C:28]([C:33]2[N:37]([CH:38]([CH3:40])[CH3:39])[N:36]=[CH:35][CH:34]=2)=[N:29][CH:30]=[CH:31][CH:32]=1>CN(C=O)C>[OH:8][CH2:9][C:10]1[C:11]([O:17][CH2:26][C:27]2[C:28]([C:33]3[N:37]([CH:38]([CH3:40])[CH3:39])[N:36]=[CH:35][CH:34]=3)=[N:29][CH:30]=[CH:31][CH:32]=2)=[CH:12][N:13]=[CH:14][C:15]=1[OH:16]Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Procedure
A mixture of 4-((tert-butyldimethylsilyloxy)methyl)pyridine-3,5-diol (100 mg, 0.39 mmol, 2 eq.) and Cs2CO3 (381 mg, 1.17 mmol, 3 eq.) in DMF (15 mL) was stirred at rt for 30 min. To this mixture was added 3-(chloromethyl)-2-(1-isopropyl-1H-pyrazol-5-yl)pyridine hydrochloride (53 mg, 0.39 mmol, 1 eq.) at rt. The mixture was continued to stir at rt O/N, filtered, concentrated, and purified on silica gel using a mixture of EtOAc and hexanes as eluent to give 4-(hydroxymethyl)-5-((2-(1-isopropyl-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)pyridin-3-ol (36 mg, 27%) as a pale yellow oil. 1H NMR (400 MHz, CDCl3) δ 8.51 (dt, J=33.0, 16.5 Hz, 1H), 7.72 (d, J=1.6 Hz, 1H), 7.69 (s, 1H), 7.47 (s, 1H), 7.33 (s, 1H), 7.21 (dd, J=7.8, 4.8 Hz, 1H), 6.10 (d, J=1.8 Hz, 1H), 4.84 (s, 2H), 4.68 (s, 1H), 4.44 (sep, 6.6 Hz, 1H), 1.24 (d, J=6.6 Hz, 6H). LRMS (M+H+) m/z 341.1
Workup
- stirringto stir at rt O/N
- filtrationfiltered
- concentrationconcentrated
- custompurified on silica gel using
- additiona mixture of EtOAc and hexanes as eluent
Sources & evidence
- ORD record
- ord-7f6ee927e85246299f1f4569c93c15f9
- Source dataset
- uspto-grants-2015_04
- Patent number
- US09012450B2
Reaction notes
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