Methyl Glycolate → (3-Amino-5-chloro-2-cyclopropylcarbamoyl-4-methyl-thieno[2,3-b]pyridin-6-yloxy)-acetic acid methylester

Temperature

90 °C

To a solution of methyl glycolate (6.55 g, 72.7 mmol) in THF (35 ml) at room temperature is added dropwise a solution of lithium bis(trimethylsilyl)amide (1.0 M in hexanes) (36.35 ml, 36.35 mmol). The resulting mixture is stirred for 20 minutes, then treated with 3-amino-5-chloro-6-methanesulfinyl-4-methyl-thieno[2,3-b]pyridine-2-carboxylic acid cyclopropylamide (5.0 g, 14.54 mmol). The reaction vessel is sealed and heated at 90° C. for 3 hours. The reaction is cooled to room temperature and quenched by the addition of water (50 ml). The mixture is partitioned between water and EtOAc (250 ml each), and the layers are shaken and separated. The aqueous layer is extracted with 2×100 ml of EtOAc. The combined organic layers are dried (anhydrous magnesium sulfate), filtered, concentrated, and flashed (1:1 hexane:EtOAc) to give the title compound as a yellow solid (3.1 g, 58%). Mass (m/z): 370.1 (M++1), 368.0 (M+−1).

1. customThe reaction vessel is sealed
2. temperatureThe reaction is cooled to room temperature
3. customquenched by the addition of water (50 ml)
4. customThe mixture is partitioned between water and EtOAc (250 ml each)
5. stirringthe layers are shaken
6. customseparated
7. extractionThe aqueous layer is extracted with 2×100 ml of EtOAc
8. dry with materialThe combined organic layers are dried (anhydrous magnesium sulfate)
9. filtrationfiltered
10. concentrationconcentrated

ORD record

ord-de10177793ed460f83bf00d503c70af6

Source dataset

uspto-grants-2011_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08071776B2