Water → 8-Bromo-2-chloro-5,11-dihydro-11-ethyl-4-methyl-6h-dipyrido[3,2-b:2',3'-e][1,4]diazepin-6-one
Reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([C:11]([NH:13][C:14]2[C:15](Cl)=[N:16][C:17]([Cl:21])=[CH:18][C:19]=2[CH3:20])=[O:12])[C:5]([NH:8][CH2:9][CH3:10])=[N:6][CH:7]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Na+].C1COCC1.O>N1C=CC=CC=1>[Br:1][C:2]1[CH:7]=[N:6][C:5]2[N:8]([CH2:9][CH3:10])[C:15]3[N:16]=[C:17]([Cl:21])[CH:18]=[C:19]([CH3:20])[C:14]=3[NH:13][C:11](=[O:12])[C:4]=2[CH:3]=1Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Procedure
A solution of crude 5-bromo-N-(2,6-dichloro4-methyl-3-pyridinyl)-2-(ethylamino)-3-pyridinecarboxamide (77.7 g, mmol) in anhydrous pyridine (1.0 L) was heated to 50° C. A 1 M solution of NaHMDS in THF (418 mL, 418 mmol) was then added dropwise and stirring was continued for an additional 15 min. After cooling to room temperature, water (50 mL) was added and the mixture concentrated to two-thirds volume on a rotary evaporator. The residue was then poured into water (3 L). Filtration gave the title compound (23.44 g) as a tan solid. The filtrate was extracted with EtOAc (3×) and the combined extracts were washed with water and brine then dried (NgSO4), filtered and concentrated under reduced pressure. The residue was purified by flash chromatography (hexane:EtOAc, 9:1 or CHCl3) to give an additional amount of the title compound (14.06 g, for a total of 37.50 g, 50% yield for 3 steps).
Workup
- concentrationthe mixture concentrated to two-thirds volume on a rotary evaporator
- additionThe residue was then poured into water (3 L)
- filtrationFiltration
Sources & evidence
- ORD record
- ord-e91951156de448c4ad94fadd4f430e18
- Source dataset
- uspto-grants-2002_07
- Patent number
- US06420359B1
Reaction notes
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