Dimethylformamide → 6-chloro-4H-thieno[3,2-b]pyrrole-5-carboxylic acid

Temperature

25 °C

To a 20 mL vial fitted with a magnetic stir bar at 25° C. was added 4H-thieno[3,2-b]pyrrole-5-carboxylic acid (0.1 g, 0.599 mmol, 1 equiv) and 2 mL of anhydrous DMF. N-chlorosuccinimide (NCS) (0.08 g, 0.599 mmol, 1 equiv) was subsequently added and the reaction vessel contents stirred for 1 h at 25° C. before heating the reaction vial to 55° C. for 12 h. The reaction was then allowed to cool to 25° C. and was diluted with EtOAc (10 mL). The resulting mixture was then washed with water) 3×5 mL). The organic phase was dried over anhydrous MgSO4, filtered, and evaporated in vacuo. The resulting residue was dissolved in a small volume of methanol, filtered through a 0.45 micron syringe filter, and further purified via preparative HPLC using the Chromeleon purification system. A 0.1% formic acid/1% acetonitrile mixture in water (aqueous phase) and methanol (no modifier added—organic phase) using a 50 mm Dynamax HPLC C-18 column at 28 mL/min (initial gradient of 40% methanol and increasing to 100% over 7 min) afforded the desired 6-chloro-4H-thieno[3,2-b]pyrrole-5-carboxylic acid 70 (5.5 mg, 5%). LC/MS m/e 199.9 (M−H). tR of product: 2.3-2.7 min. 1H NMR (400 MHz, CD3OD) δ ppm 7.41 (d, J=5.32 Hz, 1H), 6.97 (d, J=5.27 Hz, 1H).

1. customTo a 20 mL vial fitted with a magnetic stir bar at 25° C.
2. temperaturebefore heating
3. customthe reaction vial to 55° C. for 12 h
4. temperatureto cool to 25° C.
5. washThe resulting mixture was then washed with water) 3×5 mL)
6. dry with materialThe organic phase was dried over anhydrous MgSO4
7. filtrationfiltered
8. customevaporated in vacuo
9. dissolutionThe resulting residue was dissolved in a small volume of methanol
10. filtrationfiltered through a 0.45 micron syringe
11. filtrationfilter
12. customfurther purified via preparative HPLC
13. customthe Chromeleon purification system
14. temperatureincreasing to 100% over 7 min)

ORD record

ord-4e7aff7340af41bda92854328ca2c7a4

Source dataset

uspto-grants-2011_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07884124B2