Nevirapine → 11-cyclopropyl-5,11-dihydro-5-hydroxy-4-methyl-6H-dipyrido[3,2-b:2',3'-e][1,4]diazepin-6-one
Reaction equation
[CH:1]1([N:4]2[C:10]3[N:11]=[CH:12][CH:13]=[CH:14][C:9]=3[C:8](=[O:15])[NH:7][C:6]3[C:16]([CH3:20])=[CH:17][CH:18]=[N:19][C:5]2=3)[CH2:3][CH2:2]1.[H-].[Na+].[O:23]1CCCC1>>[CH:1]1([N:4]2[C:10]3[N:11]=[CH:12][CH:13]=[CH:14][C:9]=3[C:8](=[O:15])[N:7]([OH:23])[C:6]3[C:16]([CH3:20])=[CH:17][CH:18]=[N:19][C:5]2=3)[CH2:3][CH2:2]1Participants
Procedure
To a mixture of 0.5 g of 11-cyclopropyl-5,11-dihydro-4-methyl-6H-dipyrido[3,2-b:2',3'-e][1,4]diazepin-6-one (Example 12) in 25 ml of tetrahydrofuran was added 0.12 g of 50% sodium hydride in mineral oil. The reaction mixture was stirred at room temperature for one hour and then cooled to 0° C., at which time 0.9 g of oxodiperoxymolybdenum(pyridine)hexamethylphosphoramide (MoOPH) was added in one portion. The reaction mixture was then allowed to warm to room temperature and was allowed to stir overnight. The mixture was quenched with water and the solvents removed in vacuo. The residue was extracted with warm ethyl acetate, concentrated in vacuo and purified on a silica gel column (eluent: ethyl acetate) to give 0.05 g of pure 11-cyclopropyl-5,11-dihydro-5-hydroxy-4-methyl-6H-dipyrido[3,2-b:2',3'-e][1,4]diazepin-6-one, m.p. 239°-241° C. The yield was 9.5% of theory.
Workup
- additionwas added in one portion
- temperatureto warm to room temperature
- stirringto stir overnight
- customThe mixture was quenched with water
- customthe solvents removed in vacuo
- extractionThe residue was extracted with warm ethyl acetate
- concentrationconcentrated in vacuo
- custompurified on a silica gel column (eluent: ethyl acetate)
Sources & evidence
- ORD record
- ord-2f7034745b2f470c89708a8a8e8023e0
- Source dataset
- uspto-grants-1994_11
- Patent number
- US05366972
Reaction notes
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