Methanol → Nevirapine

HRID 1840630Notes

Reaction equation

HRID 1840630 reaction equation
Cl[C:2]1[C:7]([NH:8][C:9]([C:11]2[C:12]([NH:17][CH:18]3[CH2:20][CH2:19]3)=[N:13][CH:14]=[CH:15][CH:16]=2)=[O:10])=[C:6]([CH3:21])[CH:5]=[CH:4][N:3]=1.C[Si](C)(C)N[Si](C)(C)C.[Na].C[Si]([N-][Si](C)(C)C)(C)C.[Na+].CO.O>C1COCC1>[CH3:21][C:6]1[CH:5]=[CH:4][N:3]=[C:2]2[N:17]([CH:18]3[CH2:20][CH2:19]3)[C:12]3[N:13]=[CH:14][CH:15]=[CH:16][C:11]=3[C:9](=[O:10])[NH:8][C:7]=12

Participants

7

Reactant 5

HCID 887MethanolHCID 962WaterHCID 2724254Sodium bis(trimethylsilyl)amideHCID 9972204N-(2-Chloro-4-methylpyridin-3-yl)-2-(cyclopropylamino)nicotinamideHCID 45051731Sodium hexamethyidisilazane

Product 1

HCID 4463Nevirapine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
64.5 °C

Procedure

A reaction flask equipped with a magnetic stirrer, temperature controller thermodouple, addition funnel and condenser with an oil bubbler for exclusion of ambient air was inerted with nitrogen and charged with 3.02 g (0.010 mol) of N-(2-chloro-4-methyl-3-pyridinyl)-2-(cyclopropylamino)-3-pyridinecarboxamide from Example 4 and 30 ml of anhydrous THF. A 40% solution of sodium hexamethyldisilazane in THF (12.7 ml, 0.025 mol) was added dropwise maintaining the temperature of the reaction mixture at no more than 30° C. When the addition of the NaHMDS solution was completed, the reaction mixture was heated to reflux temperature (about 63-66° C.). When the reaction was completed (HPLC analysis), the mixture was cooled to ambient temperature. The reaction mixture was treated with 1.55 g (0.050 mol) of methanol and 0.45 g of water (0.025 mol). The mixture was concentrated on a rotary evaporator at 25-30 in. Hg with a 50-60° water bath temperature. The residual product weighing 4.44 g was triturated with 50 ml of water and the pH 10-12 solution was acidified to pH 3 by adding 10% HCl solution. The solid product was collected by filtration and the filter cake rinsed three times with 10 ml portions of water. The filter cake was dried in a vacuum oven at 50-60° C. to obtain nevirapine.

Workup

  1. customA reaction flask equipped with a magnetic stirrer
  2. additiontemperature controller thermodouple, addition funnel and condenser with an oil bubbler for exclusion of ambient air
  3. temperaturemaintaining the temperature of the reaction mixture at no more than 30° C
  4. temperaturethe reaction mixture was heated
  5. temperaturethe mixture was cooled to ambient temperature
  6. concentrationThe mixture was concentrated on a rotary evaporator at 25-30 in
  7. customwith a 50-60°
  8. customwas triturated with 50 ml of water
  9. additionby adding 10% HCl solution
  10. filtrationThe solid product was collected by filtration
  11. washthe filter cake rinsed three times with 10 ml portions of water
  12. customThe filter cake was dried in a vacuum oven at 50-60° C.

Sources & evidence

ORD record
ord-18f76d78c90541c282a585726e768e6c
Source dataset
uspto-grants-2004_01
Patent number
US06680383B1

Reaction notes

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