Hydrochloric Acid → Saxagliptin hydrochloride

HRID 1483179Notes

Reaction equation

HRID 1483179 reaction equation
[ClH:1].C([NH:21][C@@H:22]([C:33]12[CH2:42][CH:37]3[CH2:38][CH:39]([CH2:41][C:35]([OH:43])([CH2:36]3)[CH2:34]1)[CH2:40]2)[C:23]([N:25]1[C@H:30]([C:31]#[N:32])[CH2:29][C@H:28]2[C@@H:26]1[CH2:27]2)=[O:24])(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C(OCC)(=O)C>CO>[CH2:29]1[C@@H:30]([C:31]#[N:32])[N:25]([C:23]([C@@H:22]([NH2:21])[C:33]23[CH2:34][C:35]4([OH:43])[CH2:41][CH:39]([CH2:38][CH:37]([CH2:36]4)[CH2:42]2)[CH2:40]3)=[O:24])[C@@H:26]2[C@H:28]1[CH2:27]2.[ClH:1]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 8857Ethyl AcetateHCID 121454409(1S,3S,5S)-2-((2S)-2-(3-Hydroxyadamantan-1-yl)-2-(tritylamino)acetyl)-2-azabicyclo[3.1.0]hexane-3-carbonitrile

Product 1

HCID 49800073Saxagliptin hydrochlorideYield 95.1%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Conditions

Temperature
25 °C

Procedure

A mixture of aqueous hydrochloric acid (34.5% w/w) (2.3 g) and methanol (20 ml) was added to a mixture of (1S,3S,5S)-2-[(2S)-2-tritylamino-2-(3-hydroxyadamantan-1-yl)acetyl]-2-azabicyclo[3.1.0]hexane-3-carbonitrile (10.0 g) in methanol (80 ml), and the mass was stirred at 25° C. for 3 hours. Completion of the reaction was verified by HPLC. Solvent was distilled from the reaction mixture to give a residue. Ethyl acetate (100 ml) was mixed with the residue for 30 minutes at ambient temperature. The solid was filtered and washed with ethyl acetate (2×5 ml). The solid was dried under vacuum at 50-60° C. for 8 hours to give the title product (6.0 g). (Yield=90%; HPLC purity=99.5%)

Workup

  1. distillationSolvent was distilled from the reaction mixture
  2. customto give a residue
  3. filtrationThe solid was filtered
  4. washwashed with ethyl acetate (2×5 ml)
  5. customThe solid was dried under vacuum at 50-60° C. for 8 hours

Sources & evidence

ORD record
ord-5d729dd065bc439da20bd41d5941076b
Source dataset
uspto-grants-2016_08
Patent number
US09416105B2

Reaction notes

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