Hydrochloric Acid → Rilpivirine hydrochloride

HRID 589559Notes

Reaction equation

HRID 589559 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4](/[CH:25]=[CH:26]/[C:27]#[N:28])[CH:5]=[C:6]([CH3:24])[C:7]=1[NH:8][C:9]1[CH:10]=[CH:11][N:12]=[C:13]([NH:15][C:16]2[CH:17]=[CH:18][C:19]([C:22]#[N:23])=[CH:20][CH:21]=2)[N:14]=1.[ClH:29]>CO.CC(C)=O>[CH3:1][C:2]1[CH:3]=[C:4](/[CH:25]=[CH:26]/[C:27]#[N:28])[CH:5]=[C:6]([CH3:24])[C:7]=1[NH:8][C:9]1[CH:10]=[CH:11][N:12]=[C:13]([NH:15][C:16]2[CH:17]=[CH:18][C:19]([C:22]#[N:23])=[CH:20][CH:21]=2)[N:14]=1.[ClH:29]

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 6451164Rilpivirine

Product 1

HCID 11711114Rilpivirine hydrochloride

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 887MethanolSolvent2×

Procedure

Rilpivirine (100 gm) was suspended in a mixture of methanol (1500 ml) and acetone (2200 ml). The contents were heated to reflux and maintained for 30 minutes at reflux to obtain a clear solution. The solution was treated with carbon and stirred for 10 minutes. The reaction mass was filtered through celite bed and then concentrated to obtain a residual solid. The residual solid was stirred for 30 minutes, filtered and then dried. To the solid thus obtained was added methanol and then the reaction mass was passed dry hydrochloride gas until the precipitation obtained at 0° C. The temperature of the reaction mass was raised to room temperature and stirred for 1 hour at room temperature. The separated solid was filtered and then dried to obtain 87.5 gm of rilpivirine hydrochloride crystalline monohydrate as an off white solid.

Workup

  1. temperatureThe contents were heated
  2. temperatureto reflux
  3. temperaturemaintained for 30 minutes
  4. temperatureat reflux
  5. customto obtain a clear solution
  6. additionThe solution was treated with carbon
  7. filtrationThe reaction mass was filtered through celite bed
  8. concentrationconcentrated
  9. customto obtain a residual solid
  10. stirringThe residual solid was stirred for 30 minutes
  11. filtrationfiltered
  12. customdried
  13. customTo the solid thus obtained
  14. customuntil the precipitation
  15. customobtained at 0° C
  16. stirringstirred for 1 hour at room temperature
  17. filtrationThe separated solid was filtered
  18. customdried

Sources & evidence

ORD record
ord-967447223b1d42d3823a9b182520719b
Source dataset
uspto-grants-2016_01
Patent number
US09233935B2

Reaction notes

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