Reaction equation
[NH2:1][CH:2]([C:4]1[N:5]=[C:6]2[S:14][CH:13]=[C:12]([CH3:15])[N:7]2[C:8](=[O:11])[C:9]=1[Br:10])[CH3:3].[C:16]([OH:26])(=[O:25])[C@H:17]([C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[OH:18]>C(O)(C)C>[OH:18][C@@H:17]([C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[C:16]([O-:26])=[O:25].[Br:10][C:9]1[C:8](=[O:11])[N:7]2[C:12]([CH3:15])=[CH:13][S:14][C:6]2=[N:5][C:4]=1[C@@H:2]([NH3+:1])[CH3:3]Participants
Conditions
- Temperature
- 72 °C
Procedure
7-(1-Aminoethyl)-6-bromo-3-methyl-5H-thiazolo[3,2-a]pyrimidin-5-one (18.8 g, 65.2 mmol) was dissolved in isopropanol (375 mL) at reflux and then (S)-(+)-mandelic acid (4.84 g, 31.8 mmol) in isopropanol (375 mL) was added dropwise to the amine solution over 35 min. The reaction mixture was allowed to cool to about 72° C. and solid precipitation was observed. The slurry was cooled to room temperature and stirred for 1 hour. The solid product was collected by filtration. The wet cake was washed with isopropanol (100 mL) and dried on the filter under suction for 1 h to give the product (S)-1-(6-bromo-3-methyl-5-oxo-5H-thiazolo[3,2-a]pyrimidin-7-yl)ethanaminium (S)-2-hydroxy-2-phenylacetate (11.9 g) as a white solid. Chiral HPLC analysis was performed on a Lux Cellulose-2, 4.6×250 mm, 5 micron column using 60% ethanol/40% hexanes as the mobile phase at a flow rate of 1 mL/min. The major enantiomer eluted at retention time 11.21 min (99.0 area %). The minor enantiomer eluted at retention time 14.31 min (0.96 area %). The e.e. of the desired product was 98.08%.
Workup
- temperatureat reflux
- customsolid precipitation
- temperatureThe slurry was cooled to room temperature
- filtrationThe solid product was collected by filtration
- washThe wet cake was washed with isopropanol (100 mL)
- customdried on the
- filtrationfilter under suction for 1 h
Sources & evidence
- ORD record
- ord-dbecb13b1b064a6c89803330cb0b588e
- Source dataset
- uspto-grants-2016_09
- Patent number
- US09434746B2
Linked notes
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