Sodium bis(trimethylsilyl)amide → 11-Descyclopropyl nevirapine

HRID 1734124Notes

Reaction equation

HRID 1734124 reaction equation
C1([NH:4][C:5]2[C:10]([C:11]([NH:13][C:14]3[C:15](OC)=[N:16][CH:17]=[CH:18][C:19]=3[CH3:20])=[O:12])=[CH:9][CH:8]=[CH:7][N:6]=2)CC1.C[Si]([N-][Si](C)(C)C)(C)C.[Na+]>N1C=CC=CC=1>[CH3:20][C:19]1[C:14]2[NH:13][C:11](=[O:12])[C:10]3[CH:9]=[CH:8][CH:7]=[N:6][C:5]=3[NH:4][C:15]=2[N:16]=[CH:17][CH:18]=1

Participants

4

Reactant 2

HCID 2724254Sodium bis(trimethylsilyl)amideHCID 104474082-(Cyclopropylamino)-N-(2-methoxy-4-methyl-3-pyridinyl)-3-pyridinecarboxamide

Product 1

HCID 2239900311-Descyclopropyl nevirapineYield 91%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
90 °C

Procedure

A solution of 2-(cyclopropylamino)-N-(2-methoxy-4-methyl-3-pyridinyl)-3-pyridinecarboxamide (0.3 g, 1 mmol) in 2 mL of dry pyridine under an argon atmosphere was treated with 2.2 mL of a 1.0M solution of NaHMDS. The solution was then warmed to 90° C. for 6 h. Upon cooling, the mixture was partitioned between EtOAc and 0.5N HCl. The EtOAc layer was then washed further with 0.5N HCl, dried (MgSO4) and concentrated. The residue was purified by flash chromatography on silica gel (1:1 EtOAc:Hexanes) to give 5,11-dihydro-4-methyl-6H-dipyrido[3,2-b:2',3'-e][1,4]diazepin-6-one in 91% yield (0.24 g).

Workup

  1. temperatureUpon cooling
  2. customthe mixture was partitioned between EtOAc and 0.5N HCl
  3. washThe EtOAc layer was then washed further with 0.5N HCl
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated
  6. customThe residue was purified by flash chromatography on silica gel (1:1 EtOAc:Hexanes)

Sources & evidence

ORD record
ord-b78133a3db324dce86651e3cca1fe614
Source dataset
uspto-grants-1996_07
Patent number
US05532358

Reaction notes

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