Hydrochloric Acid → HCID 131734729, compound

HRID 1775123Notes

Reaction equation

HRID 1775123 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(#N)C>[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

5

Reactant 3

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 9926791Tofacitinib

Product 1

HCID 131734729HCID 131734729, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

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 acetonitrile (10 mL). A gummy suspension was formed, which was stirred for 26 hours at 23 to 25° C. The resulting white suspension was filtered, washed with acetonitrile (2×5 mL) and air-dried to yield 570 mg of tofacitinib hydrochloride as a white solid. 1H NMR analysis showed a molar ratio of tofacitinib hydrochloride to acetonitrile of approximately 1:0.08 (0.9 wt %). A PXRD taken of this sample is shown in FIG. 7. A sample was further dried at 58° C. at 40 torr for 24 hours. 1H NMR analysis showed a molar ratio of tofacitinib hydrochloride to acetonitrile of approximately 1:0.01 (0.1 wt %). Water content (KF) was 0.57%. The PXRD remained the same as shown in FIG. 7.

Workup

  1. customA gummy suspension was formed
  2. filtrationThe resulting white suspension was filtered
  3. washwashed with acetonitrile (2×5 mL)
  4. customair-dried

Sources & evidence

ORD record
ord-5050d575cc0449d8ad23b31b805f4187
Source dataset
uspto-grants-2016_02
Patent number
US09260438B2

Reaction notes

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