Hydrochloric Acid → HCID 131734729, compound

HRID 1775121Notes

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>CN(C)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

Conditions

Temperature: 24 °C

Procedure

A solution of 4M hydrogen chloride in 1,4-dioxane (g, 2.353 mmol) was added to a suspension of tofacitinib free base (0.7 g, 2.24 mmol) in N,N-dimethylformamide (3 mL). The clear solution was stirred at 23 to 25° C. (3 hours) without any solid formation. Ethyl acetate (2 mL) was added and the resulting turbid solution was stirred at room temperature (16 hours) resulting in the formation of a white suspension. An additional portion (5 mL) of ethyl acetate was added and stirring was continued at 23 to 25° C. for 7 hours. The white suspension was filtered, washed with ethyl acetate (2×5 mL) and air-dried for 16 hours to yield tofacitinib hydrochloride (860 mg). 1H NMR analysis showed a molar ratio of tofacitinib hydrochloride to N,N-dimethylformamide of approximately 1:0.8 (14.3 wt %). A PXRD taken of this sample is shown in FIG. 4.

Workup

stirringthe resulting turbid solution was stirred at room temperature (16 hours)
customresulting in the formation of a white suspension
stirringstirring
waitwas continued at 23 to 25° C. for 7 hours
filtrationThe white suspension was filtered
washwashed with ethyl acetate (2×5 mL)
customair-dried for 16 hours

Sources & evidence

ORD record: ord-2e770ffdd970432cbefad4df71097f6f
Source dataset: uspto-grants-2016_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09260438B2

Reaction notes

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