Sodium hydride → Nevirapine

HRID 1840631Notes

Reaction equation

HRID 1840631 reaction equation
[H-].[Na+].Cl[C:4]1[C:9]([NH:10][C:11]([C:13]2[C:14]([NH:19][CH:20]3[CH2:22][CH2:21]3)=[N:15][CH:16]=[CH:17][CH:18]=2)=[O:12])=[C:8]([CH3:23])[CH:7]=[CH:6][N:5]=1.[H][H]>COCCOCCOC.O.C(O)(=O)C>[CH3:23][C:8]1[CH:7]=[CH:6][N:5]=[C:4]2[N:19]([CH:20]3[CH2:22][CH2:21]3)[C:14]3[N:15]=[CH:16][CH:17]=[CH:18][C:13]=3[C:11](=[O:12])[NH:10][C:9]=12

Participants

7

Reactant 3

HCID 24758Sodium hydrideHCID 9972204N-(2-Chloro-4-methylpyridin-3-yl)-2-(cyclopropylamino)nicotinamideHCID 178418361HCID 178418361, compound2×

Product 1

HCID 4463NevirapineYield 96.8%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 962WaterSolvent3×HCID 8150DiglymeSolvent2×

Conditions

Temperature
130 °C

Procedure

A 500 ml 4NRB flask with stirrer, temperature controller thermocouple, addition funnel and condenser with an oil bubbler to exclude air was inserted with nitrogen and charged with 15.00 g of 60% sodium hydride in a mineral oil slurry and 120 ml of diglyme. The mixture was heated to 130° C. and treated dropwise with a solution of 41.7 g (0.138 mol) of N-(2-chloro-4-methyl-3-pyridinyl)-2-(cyclopropylamino)-3-pyridinecarboxamide, from example 4, in 70 ml of diglyme at 80 ° C. The reaction mixture was heated at 130° C. until hydrogen evolution ceased. The mixture was cooled to ambient temperature and water (6.75 g) was added dropwise cautiously. When hydrogen evolution ceased, an additional 100 ml of water was added. Acetic acid (20 ml) was added to reduce the pH of the mixture from 11-13 to about 7. An additional 100 ml of water was added and the reaction mixture stirred under ambient conditions for 30 minutes while the product crystallized. The solid product was collected by filtration and the filter cake rinsed with 100 ml of water followed by 50 ml of cyclohexane to remove any residual mineral oil from the mineral oil-sodium hydride slurry. The wet cake was dried in a vacuum oven at 50° C. for 18 hours to obtain 35.58 g of nevirapine.

Workup

  1. additionA 500 ml 4NRB flask with stirrer, temperature controller thermocouple, addition funnel and condenser with an oil bubbler
  2. temperatureThe mixture was cooled to ambient temperature
  3. customcrystallized
  4. filtrationThe solid product was collected by filtration
  5. washthe filter cake rinsed with 100 ml of water
  6. customto remove any residual mineral oil from the mineral oil-sodium hydride slurry
  7. customThe wet cake was dried in a vacuum oven at 50° C. for 18 hours

Sources & evidence

ORD record
ord-af074fad0c4746a8b3e4e4cb2daf4247
Source dataset
uspto-grants-2004_01
Patent number
US06680383B1

Reaction notes

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