Methanol → Nelfinavir Mesylate

HRID 384737Notes

Reaction equation

HRID 384737 reaction equation
[CH3:1][C:2]1[C:7]([OH:8])=[CH:6][CH:5]=[CH:4][C:3]=1[C:9]([NH:11][C@H:12]([C@H:21]([OH:40])[CH2:22][N:23]1[C@H:32]([C:33]([NH:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[CH2:31][C@H:30]2[C@H:25]([CH2:26][CH2:27][CH2:28][CH2:29]2)[CH2:24]1)[CH2:13][S:14][C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1)=[O:10].CO.[CH3:43][S:44]([OH:47])(=[O:46])=[O:45].CC(=O)CCC>C(C(C)=O)C(C)C.C(C(C)=O)C.CC(C)=O.C1COCC1.C(O)(C)C.C(O)C>[CH3:1][C:2]1[C:7]([OH:8])=[CH:6][CH:5]=[CH:4][C:3]=1[C:9]([NH:11][C@H:12]([C@H:21]([OH:40])[CH2:22][N:23]1[C@H:32]([C:33]([NH:35][C:36]([CH3:38])([CH3:37])[CH3:39])=[O:34])[CH2:31][C@H:30]2[C@H:25]([CH2:26][CH2:27][CH2:28][CH2:29]2)[CH2:24]1)[CH2:13][S:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)=[O:10].[CH3:43][S:44]([OH:47])(=[O:46])=[O:45]

Participants

11

Reactant 4

HCID 887MethanolHCID 6395Methanesulfonic AcidHCID 78952-PentanoneHCID 64143Nelfinavir

Product 1

HCID 64142Nelfinavir Mesylate

Reagents, catalysts & solvents 6

HCID 180AcetoneSolventHCID 702EthanolSolventHCID 3776IsopropanolSolventHCID 6569Methyl Ethyl KetoneSolventHCID 7909Methyl Isobutyl KetoneSolventHCID 8028TetrahydrofuranSolvent

Procedure

Thus in accordance to the present invention Nelfinavir base is suspended in an organic solvent, selected from methanol, ethanol, isopropanol, THF, and methanesulfonic acid is added at temperature below 45° C. over a period of 10 min to 4 hrs. The reaction mass is mixed for about 15 min to 4 hrs to form a solution and then cooled to 10° C. to 35° C. A ketone such as acetone, methyl ethyl ketone, methyl isobutyl ketone, 2-pentanone is added as ante solvent at temperature 10° C. to about 35° C. in about 15 min to 4 hrs. The resulting reaction mass is maintained at temperature of 10° C. to 35° C. for about 30 min to 6 hrs then cooled and maintained at temperature of −10° C. to 15° C. for about 30 min to 4 hrs. The precipitated solid is separated and dried at temperature of 50° C. to 120° C., preferably at 80° C. to 110° C. under reduced pressure to produce novel crystalline forms of Nelfinavir mesylate.

Workup

  1. additionis added at temperature below 45° C. over a period of 10 min to 4 hrs
  2. additionThe reaction mass is mixed for about 15 min to 4 hrs
  3. customto form a solution
  4. temperaturecooled to 10° C. to 35° C
  5. customThe resulting reaction mass
  6. temperatureis maintained at temperature of 10° C. to 35° C. for about 30 min to 6 hrs
  7. temperaturethen cooled
  8. temperaturemaintained at temperature of −10° C. to 15° C. for about 30 min to 4 hrs
  9. customThe precipitated solid is separated
  10. customdried at temperature of 50° C. to 120° C., preferably at 80° C. to 110° C. under reduced pressure

Sources & evidence

ORD record
ord-40481b481c004547be741942f60be281
Source dataset
uspto-grants-2013_02
Patent number
US08367832B2

Reaction notes

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