Toluene → 2,6-Lutidine
Reaction equation
[C:1]1([CH3:7])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C([N:10](CC)CC)C.[P:15]([Cl:19])([Cl:18])([Cl:17])=[O:16]>>[P:15]([Cl:19])([Cl:18])([Cl:17])=[O:16].[N:10]1[C:5]([CH3:6])=[CH:4][CH:3]=[CH:2][C:1]=1[CH3:7]Participants
Procedure
Intermediate 1(b) may then be cyclized to the 6-chloro-purine intermediate 1(c) by treatment with a condensation agent using analogous procedures and conditions described in U.S. Pat. No.4,728,644, incorporated herein by reference. In a preferred method, intermediate 1(b) can be refluxed in a weak acid (e.g., acetic acid) or sulfuric acid in an appropriate solvent (e.g., isopropyl alcohol, toluene) to provide the hydroxy purine intermediate 1(d) followed by refluxing in phosphorous oxychloride, toluene in the presence of phosphorous oxychloride and triethylamine, or 2,6-lutidine in phosphorous oxychloride to give intermediate 1(c). In another preferred method, 1(b) may be directly converted to 1(c) by refluxing in phosphorous oxychloride; an appropriate co-solvent (e.g., toluene) and/or base (e.g., pyridine, triethylamine) may be added to aid in the condensation.
Sources & evidence
- ORD record
- ord-d575a7e369274d9dab5940abd6c7b603
- Source dataset
- uspto-grants-2006_10
- Patent number
- US07129239B2
Reaction notes
Loading…