Methane → Rilpivirine hydrochloride

HRID 2280430Notes

Reaction equation

HRID 2280430 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.C.[ClH:30]>CO.C(C(C)=O)C.C(O)(C)C>[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:30]

Participants

7

Reactant 3

HCID 297MethaneHCID 313Hydrochloric AcidHCID 6451164Rilpivirine

Product 1

HCID 11711114Rilpivirine hydrochloride

Reagents, catalysts & solvents 3

HCID 887MethanolSolvent2×HCID 3776IsopropanolSolventHCID 6569Methyl Ethyl KetoneSolvent

Conditions

Temperature
62.5 °C

Procedure

Rilpivirine (20 gm; Chromatographic purity: 96.5%) was suspended in a mixture of methanol and methyl ethyl ketone (1:1, 2000 ml) and then heated to reflux for 1 hour to provide a clear solution. The solution was treated with charcoal and filtered through celite bed. The solvent was distilled off under reduced pressure to obtain a residual solid. To the residual solid was added methanol (200 ml) and then heated to 60 to 65° C. To the solution was added a solution of hydrochloric acid in isopropanol (200 ml) at 60 to 65° C. and stirred for 1 hour 30 minutes. The contents were cooled to room temperature and stirred for 30 minutes. The separated solid was filtered and then dried to provide 14 gm of rilpivirine hydrochloride.

Workup

  1. temperatureheated
  2. temperatureto reflux for 1 hour
  3. customto provide a clear solution
  4. filtrationfiltered through celite bed
  5. distillationThe solvent was distilled off under reduced pressure
  6. customto obtain a residual solid
  7. temperatureThe contents were cooled to room temperature
  8. stirringstirred for 30 minutes
  9. filtrationThe separated solid was filtered
  10. customdried

Sources & evidence

ORD record
ord-83b3be3bfaaa40a09965ecec7c8f2a08
Source dataset
uspto-grants-2015_09
Patent number
US09139535B2

Reaction notes

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