Hydrochloric Acid → Dapivirine

HRID 2305421Notes

Reaction equation

HRID 2305421 reaction equation
Cl[C:2]1[N:7]=[C:6]([NH:8][C:9]2[C:14]([CH3:15])=[CH:13][C:12]([CH3:16])=[CH:11][C:10]=2[CH3:17])[CH:5]=[CH:4][N:3]=1.Cl.CC(O)C.[NH2:23][C:24]1[CH:31]=[CH:30][C:27]([C:28]#[N:29])=[CH:26][CH:25]=1.C([O-])(O)=O.[Na+]>O>[CH3:17][C:10]1[CH:11]=[C:12]([CH3:16])[CH:13]=[C:14]([CH3:15])[C:9]=1[NH:8][C:6]1[CH:5]=[CH:4][N:3]=[C:2]([NH:23][C:24]2[CH:31]=[CH:30][C:27]([C:28]#[N:29])=[CH:26][CH:25]=2)[N:7]=1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 3776IsopropanolHCID 133964-AminobenzonitrileHCID 516892Sodium BicarbonateHCID 223984242-Chloro-N-(2,4,6-trimethylphenyl)-4-pyrimidinamine

Product 1

HCID 214347DapivirineYield 86%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
42.5 °C

Procedure

A mixture of intermediate 49 (0.082 mol) and 5.4 N HCl in 2-propanol (0.086 mol) in water (300 ml) was stirred and warmed to 40-45° C. over 30 minutes. 4-Amino-benzonitrile (0.242 mol) was added at 40-45° C. The reaction mixture was stirred and refluxed for 4.5 hours, then cooled to room temperature. The mixture was alkalized by portionwise addition of NaHCO3. This mixture was extracted with ethylacetate. The organic layer was separated, washed with brine, dried, filtered, and the solvent was evaporated. This fraction was stirred in ethanol p.a. (100 ml), filtered off, washed with ethanol (50 ml), then dried, yielding 23.1 g (86%) 4-[[4-[(2,4,6-trimethylphenyl)amino]-2-pyrimidinyl]amino]benzonitrile (compound 52).

Workup

  1. stirringThe reaction mixture was stirred
  2. temperaturerefluxed for 4.5 hours
  3. temperaturecooled to room temperature
  4. extractionThis mixture was extracted with ethylacetate
  5. customThe organic layer was separated
  6. washwashed with brine
  7. customdried
  8. filtrationfiltered
  9. customthe solvent was evaporated
  10. stirringThis fraction was stirred in ethanol p.a
  11. filtration(100 ml), filtered off
  12. washwashed with ethanol (50 ml)
  13. customdried

Sources & evidence

ORD record
ord-c07c41ce77d9461e843893d6efe37bb3
Source dataset
uspto-grants-2002_08
Patent number
US06440986B2

Reaction notes

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