Methanol → 1,3-Dihydroxy-2-(hydroxymethyl)propan-2-aminium 2-((3S,4R)-4-{[(3,4-dichloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-fluoropiperidin-1-yl)-1,3-thiazole-5-carboxylate

Temperature

60 °C

Tromethamine (43 mg, 0.36 mmol), 2-((3S,4R)-4-{[(3,4-dichloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-fluoropiperidin-1-yl)-1,3-thiazole-5-carboxylic acid (Example 42, 150 mg, 0.36 mmol), methanol (50 ml) and water (5 ml) were combined and stirred at 60° C. until the mixture was a homogeneous solution (30 min). The mixture was cooled to room temperature and concentrated under reduced pressure. The crude salt (80 mg) was dissolved in ethyl acetate/methanol (8 ml; 50:50) and ethyl acetate was added slowly to the stirred solution until it became cloudy. Stirring was continued and additional ethyl acetate (˜15 ml) was added slowly to the mixture. The mixture was stored at 4° C. overnight. The solid was collected by filtration and air dried for 24 h to provide the salt (64 mg).

1. customa homogeneous solution (30 min)
2. temperatureThe mixture was cooled to room temperature
3. concentrationconcentrated under reduced pressure
4. dissolutionThe crude salt (80 mg) was dissolved in ethyl acetate/methanol (8 ml; 50:50)
5. additionethyl acetate was added slowly to the stirred solution until it
6. stirringStirring
7. additionadditional ethyl acetate (˜15 ml) was added slowly to the mixture
8. filtrationThe solid was collected by filtration and air
9. customdried for 24 h

ORD record

ord-fde65061ac904aedb646d060ad1f49ec

Source dataset

uspto-grants-2013_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08399489B2