Hydrochloric Acid → HCID 131734729, compound

HRID 1775120Notes

Reaction equation

HRID 1775120 reaction equation
[ClH:1].C(O)(C)C.[CH3:6][C@H:7]1[C@@H:12]([N:13]([C:15]2[N:23]=[CH:22][N:21]=[C:20]3[C:16]=2[CH:17]=[CH:18][NH:19]3)[CH3:14])[CH2:11][N:10]([C:24]([CH2:26][C:27]#[N:28])=[O:25])[CH2:9][CH2:8]1>CC(C)=O>[CH3:6][C@H:7]1[C@@H:12]([N:13]([C:15]2[N:23]=[CH:22][N:21]=[C:20]3[C:16]=2[CH:17]=[CH:18][NH:19]3)[CH3:14])[CH2:11][N:10]([C:24]([CH2:26][C:27]#[N:28])=[O:25])[CH2:9][CH2:8]1.[ClH:1]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 3776IsopropanolHCID 9926791Tofacitinib

Product 1

HCID 131734729HCID 131734729, compound

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Conditions

Temperature
45 °C

Procedure

A solution of approximately 17 wt % hydrogen chloride in isopropanol (7.684 mmol) was added to a suspension of tofacitinib free base (2.0 g, 6.402 mmol) in acetone (28 mL). The suspension was heated to 45° C. for 4 hours and then cooled to 23 to 25° C. Small amounts of solids were adhered to the walls of the flask which were broken with a spatula. The white suspension was stirred at 23 to 25° C. for 22 hours, filtered, washed with acetone (2×10 mL) and dried under vacuum (5 torr) at 40° C. (3 hours) to yield tofacitinib hydrochloride (2.36 g) as a white solid. 1H NMR analysis showed a molar ratio of tofacitinib hydrochloride to acetone of approximately 1:0.82 (12.0 wt %). Water content (KF) was 1.89%. A PXRD taken of the sample is shown in FIG. 3.

Workup

  1. temperaturecooled to 23 to 25° C
  2. filtrationfiltered
  3. washwashed with acetone (2×10 mL)
  4. customdried under vacuum (5 torr) at 40° C. (3 hours)

Sources & evidence

ORD record
ord-051abf4f23c74713b2e04309ed946e31
Source dataset
uspto-grants-2016_02
Patent number
US09260438B2

Reaction notes

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