6-Desamino 6-Chloro Etravirine → Etravirine

HRID 1796949Notes

Reaction equation

HRID 1796949 reaction equation
[Br:1][C:2]1[C:3]([O:18][C:19]2[C:24]([CH3:25])=[CH:23][C:22]([C:26]#[N:27])=[CH:21][C:20]=2[CH3:28])=[N:4][C:5]([NH:9][C:10]2[CH:17]=[CH:16][C:13]([C:14]#[N:15])=[CH:12][CH:11]=2)=[N:6][C:7]=1Cl.[NH3:29].O1CCOCC1>O>[NH2:29][C:7]1[C:2]([Br:1])=[C:3]([O:18][C:19]2[C:24]([CH3:25])=[CH:23][C:22]([C:26]#[N:27])=[CH:21][C:20]=2[CH3:28])[N:4]=[C:5]([NH:9][C:10]2[CH:17]=[CH:16][C:13]([C:14]#[N:15])=[CH:12][CH:11]=2)[N:6]=1

Participants

4

Reactant 2

HCID 117514166-Desamino 6-Chloro EtravirineHCID 66648793Ammonia dioxane

Product 1

HCID 193962EtravirineYield 40.5%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

4-[[5-bromo-4-(4-cyano-2,6-dimethylphenoxy)-6-chloro-2-pyrimidinyl]amino]-benzonitrile (0.00250 mol) and NH3/1,4-dioxane 0.5M (0.015 mol) were heated in a pressure vessel at 150° C. for 4 days. The sample was allowed to sit at ambient conditions for 2 days. Water was added slowly to the mixture until a precipitate formed. The mixture was stirred for 2 hours and filtered. The solid was recrystallized from CH3CN to obtain 0.58 g (fraction 1). The filtrate was evaporated (fraction 2). Both fractions were combined and purified by column chromatography, eluting with CH2Cl2. The resulting residue of the desired fraction was recrystallized from CH3CN to yield 0.44 g of 4-[[4-amino-5-bromo-6-(4-cyano-2,6-dimethylphenyloxy)-2-pyrimidinyl]amino]benzonitrile (40.5%). The sample was dried at 80° C. for 16 hours at 0.2 mm Hg (interm. 30). 4-[[4-amino-5-chloro-6-(4-cyano-2,6-dimethylphenyloxy)-2-pyrimidinyl]amino]benzonitrile (interm. 31) was prepared according to an analogous procedure.

Workup

  1. customformed
  2. filtrationfiltered
  3. customThe solid was recrystallized from CH3CN
  4. customto obtain 0.58 g (fraction 1)
  5. customThe filtrate was evaporated (fraction 2)
  6. custompurified by column chromatography
  7. washeluting with CH2Cl2
  8. customThe resulting residue of the desired fraction was recrystallized from CH3CN

Sources & evidence

ORD record
ord-2f88d077e471453f94d5a980e39c97d4
Source dataset
uspto-grants-2006_04
Patent number
US07034019B2

Reaction notes

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