Hydrochloric Acid → HCID 131734729, compound

HRID 1775122Notes

Reaction equation

HRID 1775122 reaction equation
[ClH:1].O1CCOCC1.[CH3:8][C@H:9]1[C@@H:14]([N:15]([C:17]2[N:25]=[CH:24][N:23]=[C:22]3[C:18]=2[CH:19]=[CH:20][NH:21]3)[CH3:16])[CH2:13][N:12]([C:26]([CH2:28][C:29]#[N:30])=[O:27])[CH2:11][CH2:10]1.C(OCC)(=O)C>CS(C)=O>[CH3:8][C@H:9]1[C@@H:14]([N:15]([C:17]2[N:25]=[CH:24][N:23]=[C:22]3[C:18]=2[CH:19]=[CH:20][NH:21]3)[CH3:16])[CH2:13][N:12]([C:26]([CH2:28][C:29]#[N:30])=[O:27])[CH2:11][CH2:10]1.[ClH:1]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 8857Ethyl AcetateHCID 312751,4-DioxaneHCID 9926791Tofacitinib

Product 1

HCID 131734729HCID 131734729, compound

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
24 °C

Procedure

A solution of 4M hydrogen chloride in 1,4-dioxane (2.353 mmol) was added to a suspension of tofacitinib free base (0.7 g, 2.24 mmol) in dimethyl sulfoxide (3 mL). The clear solution was stirred at 23 to 25° C. (16 hours) without any solid formation. Ethyl acetate (17 mL) was added and the resulting white suspension was heated to 45° C. (2 hours) and cooled to 23 to 25° C. over 4 hours. The white suspension was filtered, washed with ethyl acetate (2×5 mL) and air-dried for 16 hours to yield 830 mg of tofacitinib hydrochloride as a white solid. 1H NMR analysis showed a molar ratio of tofacitinib hydrochloride to dimethyl sulfoxide of approximately 1:1 (18.3 wt %). A PXRD taken of this sample is shown in FIG. 5.

Workup

  1. temperaturethe resulting white suspension was heated to 45° C. (2 hours)
  2. temperaturecooled to 23 to 25° C. over 4 hours
  3. filtrationThe white suspension was filtered
  4. washwashed with ethyl acetate (2×5 mL)
  5. customair-dried for 16 hours

Sources & evidence

ORD record
ord-8924d62f88f04ffdb1ab5440b580664e
Source dataset
uspto-grants-2016_02
Patent number
US09260438B2

Reaction notes

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