Methanol → 3-Amino-5-chloro-4-methyl-6-methylsulfanyl-thieno[2,3-b]pyridine-2-carboxylic acid cyclopropylamide

To a mixture of thioacetic acid S-cyclopropylcarbamoylmethyl ester (8.58 g, 49.5 mmol) and MeOH (100 ml) is added sodium methoxide solution (25% wt. in MeOH)(15.4 ml, 67.5 mmol). The resulting solution is stirred at room temperature for 20 minutes, then treated with 2,5-dichloro-4-methyl-6-methylsulfanyl-nicotinonitrile (10.5 g, 45.0 mmol). The mixture is refluxed at 100° C. for 2 hours, cooled to room temperature, and quenched by adding water (100 ml). The mixture is partitioned between water and EtOAc (300 ml each), and the layers are shaken and separated. The aqueous layer is extracted with EtOAc (2×150 ml). The combined organic layers are washed with brine (200 ml), dried (anhydrous magnesium sulfate), filtered, and concentrated to give an orange solid. Flash chromatography (1:1 hexane:EtOAc) affords the title compound as a yellow solid (8.4 g, 57%). Mass (m/z): 328.1 (M++1).

1. temperatureThe mixture is refluxed at 100° C. for 2 hours
2. temperaturecooled to room temperature
3. customquenched
4. additionby adding water (100 ml)
5. customThe mixture is partitioned between water and EtOAc (300 ml each)
6. stirringthe layers are shaken
7. customseparated
8. extractionThe aqueous layer is extracted with EtOAc (2×150 ml)
9. washThe combined organic layers are washed with brine (200 ml)
10. dry with materialdried (anhydrous magnesium sulfate)
11. filtrationfiltered
12. concentrationconcentrated
13. customto give an orange solid

ORD record

ord-a41ec41f64954206bd85f91a0e6df5be

Source dataset

uspto-grants-2011_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08071776B2