Hydrogen Bromide → Tofacitinib hydrobromide

HRID 1775141Notes

Reaction equation

HRID 1775141 reaction equation
[CH3:1][C@H:2]1[C@@H:7]([N:8]([C:10]2[N:18]=[CH:17][N:16]=[C:15]3[C:11]=2[CH:12]=[CH:13][NH:14]3)[CH3:9])[CH2:6][N:5]([C:19]([CH2:21][C:22]#[N:23])=[O:20])[CH2:4][CH2:3]1.[BrH:24]>CC(C)=O>[CH3:1][C@H:2]1[C@@H:7]([N:8]([C:10]2[N:18]=[CH:17][N:16]=[C:15]3[C:11]=2[CH:12]=[CH:13][NH:14]3)[CH3:9])[CH2:6][N:5]([C:19]([CH2:21][C:22]#[N:23])=[O:20])[CH2:4][CH2:3]1.[BrH:24]

Participants

4

Reactant 2

HCID 260Hydrogen BromideHCID 9926791Tofacitinib

Product 1

HCID 131734730Tofacitinib hydrobromide

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent2×

Conditions

Temperature
24 °C

Procedure

Amorphous tofacitinib free base (0.70 g, 2.24 mmol) was dissolved in acetone (3 mL). To the clear solution was charged a solution of hydrogen bromide (7.2 mL) in acetone (0.314 M, prepared by addition of 1.93 g of acetyl bromide and 0.50 g of methanol to 50 mL of acetone, 2.26 mmol) in one portion and the white suspension was stirred at 23 to 25° C. for 16 hours. The white suspension was filtered, washed with acetone (2×10 mL) and dried under vacuum (35 torr) for 16 hours to yield 0.55 g of tofacitinib hydrobromide as a white solid. 1H NMR analysis showed a molar ratio of tofacitinib hydrobromide to acetone of approximately 1:0.7 (9.4 wt %) Water content (KF) was 0.88%. A PXRD taken of this sample is shown in FIG. 18.

Workup

  1. filtrationThe white suspension was filtered
  2. washwashed with acetone (2×10 mL)
  3. customdried under vacuum (35 torr) for 16 hours

Sources & evidence

ORD record
ord-272e7770c19d4e35ac12cc28f32fd4cc
Source dataset
uspto-grants-2016_02
Patent number
US09260438B2

Reaction notes

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