Methanesulfonic Acid → Nelfinavir Mesylate

HRID 1738579Notes

Reaction equation

HRID 1738579 reaction equation
[C:1]([NH:5][C:6]([C@@H:8]1[CH2:17][C@H:16]2[C@H:11]([CH2:12][CH2:13][CH2:14][CH2:15]2)[CH2:10][N:9]1[CH2:18][C@@H:19]([OH:40])[C@@H:20]([NH:29][C:30](=[O:39])[C:31]1[CH:36]=[CH:35][CH:34]=[C:33]([OH:37])[C:32]=1[CH3:38])[CH2:21][S:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:41][S:42]([OH:45])(=[O:44])=[O:43].COC(C)(C)C>O1CCCC1>[CH3:41][S:42]([OH:45])(=[O:44])=[O:43].[C:1]([NH:5][C:6]([C@@H:8]1[CH2:17][C@H:16]2[C@H:11]([CH2:12][CH2:13][CH2:14][CH2:15]2)[CH2:10][N:9]1[CH2:18][C@@H:19]([OH:40])[C@@H:20]([NH:29][C:30](=[O:39])[C:31]1[CH:36]=[CH:35][CH:34]=[C:33]([OH:37])[C:32]=1[CH3:38])[CH2:21][S:22][C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 6395Methanesulfonic AcidHCID 15413tert-Butyl methyl etherHCID 64143Nelfinavir2×

Product 1

HCID 64142Nelfinavir MesylateYield 95.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

(3S,4aS,8aS)-2-[(2R,3R)-2-Hydroxy-3-(3-hydroxy-2-methylbenzoylamino)-4-phenylthiobutyl]decahydroisoquinoline-3-carboxylic acid t-butylamide (compound [15], 7.80 g, 13.7 mmol) was suspended in tetrahydrofuran (40 ml) and methanesulfonic acid (0.918 ml, 14.1 mmol) was added, which was stirred until the solid was completely dissolved. The mixture was dropwise added to methyl-t-butyl ether (470 ml) (after rinsing with 5 ml of tetrahydrofuran). Precipitate was produced instantaneously with the dropwise addition. The mixture was stirred at room temperature for 2 hours after the dropwise addition. The precipitate was collected by filtration, washed with methyl-t-butyl ether (27 ml) and dried at 65° C. for one day under reduced pressure to give (3S,4aS,8aS)-2-[(2R,3R)-2-hydroxy-3-(3-hydroxy-2-methylbenzoylamino)-4-phenylthiobutyl]decahydroisoquinoline-3-carboxylic acid t-butylamide methanesulfonate (8.68 g, yield 95%) as a colorless solid.

Workup

  1. dissolutionwas completely dissolved
  2. customPrecipitate was produced instantaneously with the dropwise addition
  3. stirringThe mixture was stirred at room temperature for 2 hours
  4. additionafter the dropwise addition
  5. filtrationThe precipitate was collected by filtration
  6. washwashed with methyl-t-butyl ether (27 ml)
  7. customdried at 65° C. for one day under reduced pressure

Sources & evidence

ORD record
ord-56638064fa244fb18b88695896d8b370
Source dataset
uspto-grants-1999_10
Patent number
US05962704

Reaction notes

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