Sulfuric Acid → Atazanavir Sulfate

HRID 1257098Notes

Reaction equation

HRID 1257098 reaction equation
[CH3:1][C:2]([C@H:5]([NH:47][C:48]([O:50][CH3:51])=[O:49])[C:6]([NH:8][C@H:9]([C@@H:17]([OH:46])[CH2:18][N:19]([NH:33][C:34]([C@@H:36]([NH:41][C:42]([O:44][CH3:45])=[O:43])[C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[CH2:20][C:21]1[CH:26]=[CH:25][C:24]([C:27]2[N:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)=[CH:23][CH:22]=1)[CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)=[O:7])([CH3:4])[CH3:3].[S:52](=[O:56])(=[O:55])([OH:54])[OH:53]>CCO.CCOC(C)=O>[CH3:4][C:2]([C@H:5]([NH:47][C:48]([O:50][CH3:51])=[O:49])[C:6]([NH:8][C@H:9]([C@@H:17]([OH:46])[CH2:18][N:19]([NH:33][C:34]([C@@H:36]([NH:41][C:42]([O:44][CH3:45])=[O:43])[C:37]([CH3:38])([CH3:39])[CH3:40])=[O:35])[CH2:20][C:21]1[CH:22]=[CH:23][C:24]([C:27]2[CH:28]=[CH:29][CH:30]=[CH:31][N:32]=2)=[CH:25][CH:26]=1)[CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)=[O:7])([CH3:1])[CH3:3].[OH:55][S:52]([OH:56])(=[O:54])=[O:53]

Participants

4

Reactant 2

HCID 1118Sulfuric AcidHCID 148192Atazanavir

Product 1

HCID 158550Atazanavir SulfateYield 55%

Reagents, catalysts & solvents 1

HCID 21584252Ethanol ethylacetateSolvent

Procedure

To a 20 mL sample vial equipped with a magnetic stir was charged atazanavir base (1.0 g) and a mixture of 99.5% EtOH/EtOAc (1/1, 7.5 mL, 7.5 vol) followed by concentrated sulfuric acid (0.085 mL, 1.1 equiv) at 20-30° C. The resulting clear amber solution was stirred at 20-30° C. for 4 hr. The product was filtered, washed with a mixture of EtOH/EA (1:1, 2 mL, 2 vol), and dried under vacuum at 40-50° C. for 16 hr to afford atazanavir sulfate in Form A (0.61 g, 55% yield, 99.9% HPLC purity).

Workup

  1. customTo a 20 mL sample vial equipped with
  2. stirringThe resulting clear amber solution was stirred at 20-30° C. for 4 hr
  3. filtrationThe product was filtered
  4. washwashed with a mixture of EtOH/EA (1:1, 2 mL, 2 vol)
  5. customdried under vacuum at 40-50° C. for 16 hr

Sources & evidence

ORD record
ord-a597a3576b004145a49bf35317642aed
Source dataset
uspto-grants-2013_06
Patent number
US08461347B2

Reaction notes

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