Water → Ticagrelor Impurity O

HRID 2404971Notes

Reaction equation

HRID 2404971 reaction equation
Cl[C:2]1[C:7]([N+:8]([O-:10])=[O:9])=[C:6]([Cl:11])[N:5]=[C:4]([S:12][CH2:13][CH2:14][CH3:15])[N:3]=1.[NH2:16][C@H:17]1[C@@H:21]2[O:22][C:23]([CH3:26])([CH3:25])[O:24][C@@H:20]2[C@@H:19]([O:27][CH2:28][CH2:29][OH:30])[CH2:18]1.O.C(OCC)(=O)C>O1CCCC1>[Cl:11][C:6]1[N:5]=[C:4]([S:12][CH2:13][CH2:14][CH3:15])[N:3]=[C:2]([NH:16][C@H:17]2[C@@H:21]3[O:22][C:23]([CH3:25])([CH3:26])[O:24][C@@H:20]3[C@@H:19]([O:27][CH2:28][CH2:29][OH:30])[CH2:18]2)[C:7]=1[N+:8]([O-:10])=[O:9]

Participants

6

Reactant 4

HCID 962WaterHCID 8857Ethyl AcetateHCID 99425962-[[(3aR,4S,6R,6aS)-6-Aminotetrahydro-2,2-dimethyl-4H-cyclopenta-1,3-dioxol-4-yl]oxy]ethanolHCID 222689244,6-Dichloro-5-nitro-2-(propylthio)pyrimidine

Product 1

HCID 86674064Ticagrelor Impurity OYield 45%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 4,6-dichloro-5-nitro-2-(propylthio)pyrimidine (1.07 g, 3.99 mmol, 1.00 equiv.), and 2-((3aR,4S,6R,6aS)-6-amino-2,2-dimethyl-tetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yloxy)ethanol (570 mg, 4.41 mmol, 1.20 equiv.) in tetrahydrofuran (20 mL) was stirred at 0-10° C. for about 2 hours and then water (20 mL) was added. Standard extractive workup with ethyl acetate (3×20 mL) afforded the title product as a yellow oil (800 mg; yield=45%). 1H NMR (300 MHz, CDCl3) δ: 8.65 (b, 1H), 4.66-4.76 (m, 2H), 4.56 (m, 1H), 3.99 (d, J=7.5 Hz, 1H), 3.70-3.87 (m, 3H), 3.64-3.67 (m, 1H), 3.07-3.20 (m, 2H), 2.34 (m, 1H), 1.97 (m, 1H), 1.76-1.82 (m, 2H), 1.46 (s, 3H), 1.27 (s, 3H), 1.07 (t, J=7.5 Hz, 3H).

Sources & evidence

ORD record
ord-de9683db2e084a8b8e8bae94513f0546
Source dataset
uspto-grants-2014_08
Patent number
US08802850B2

Reaction notes

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