HCID 178434040, compound → HCID 178434039, compound

HRID 1052946Notes

Reaction equation

HRID 1052946 reaction equation
[CH3:1][C:2]1[N:6]([C@H:7]2[CH2:13][C@H:12]3[N:14]([CH2:15][CH2:16][C@H:17]([NH:24][C:25]([CH:27]4[CH2:32][CH2:31][C:30]([F:34])([F:33])[CH2:29][CH2:28]4)=[O:26])[C:18]4[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=4)[C@H:9]([CH2:10][CH2:11]3)[CH2:8]2)[C:5]([CH:35]([CH3:37])[CH3:36])=[N:4][N:3]=1.C(Cl)Cl>C(OCC)(=O)C>[CH3:1][C:2]1[N:6]([C@H:7]2[CH2:13][C@H:12]3[N:14]([CH2:15][CH2:16][C@H:17]([NH:24][C:25]([CH:27]4[CH2:28][CH2:29][C:30]([F:34])([F:33])[CH2:31][CH2:32]4)=[O:26])[C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)[C@H:9]([CH2:10][CH2:11]3)[CH2:8]2)[C:5]([CH:35]([CH3:37])[CH3:36])=[N:4][N:3]=1

Participants

3

Reactant 1

HCID 178434040HCID 178434040, compound2×

Product 1

HCID 178434039HCID 178434039, compoundYield 75%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent3×

Procedure

Extraction and recrystallization of maraviroc from Selzentry® (ViiV Healthcare) was purchased through the University of Washington's Investigative Drug Services facility. Maraviroc is purified and recrystallized from Selzentry in a simple 7-step process. First, Selzentry tablets re crushed 6 at a time (1.8 g of maraviroc) by hand using a mortar and pestle. Due to the brittle nature of the pill's core and the more flexible properties of the pill's film-coat, the core is ground into a fine white powder while the film-coat remained in larger blue flakes. Second, a fine copper mesh (Home Depot) is used to separate the film-coat fragments from the interior powder. Third, 100 mL of dichloromethane (Sigma Aldrich) and 1 g of anhydrous MgSO4 (Fisher Scientific) are added to the powder and stirred with a magnetic stir bar for 10 minutes to dissolve the MVC into the dichloromethane. Fourth, this suspension is filtered through cellulose filter paper (Whatman) into a 250 mL round bottom flask. The filtrate is clear and colorless. Fifth, the dichloromethane is evaporated using a rotary evaporator (Rotovap) to produce a white foam (maraviroc-DCM polymorph). Sixth, refluxing ethyl acetate (Sigma Aldrich) is added slowly to the white foam while keeping the round bottom flask at a temperature of 70° C. Gentle swirling helped dissolve the maraviroc foam into the ethyl acetate. Once all of the maraviroc was dissolved, the round bottom flask was allowed to cool slowly to room temperature, then again to 4° C. White maraviroc crystals form in the ethyl acetate. Finally, the ethyl acetate is removed under vacuum using a rotary evaporator to yield pure and completely crystalline maraviroc. Yield is ˜75%. Identity and purity is confirmed by proton-NMR on the sample dissolved in CDCl3 (University of Washington Chemistry Supplies Store). Common contaminants (<1% molar composition) are polyethylene glycol (from pill film-coat fragments) and ethyl acetate, identified by peaks on NMR spectra. Calorimetry measurements are taken to further verify crystallinity and purity using differential scanning calorimetry (see below).

Workup

  1. additionis added slowly to the white foam
  2. customat a temperature of 70° C
  3. customagain to 4° C

Sources & evidence

ORD record
ord-a667e7e56772402f974b80ceaab90baa
Source dataset
uspto-grants-2016_07
Patent number
US09393216B2

Reaction notes

Loading…