Hydrochloric Acid → HCID 66759575, compound

Temperature

120 °C

A mixture of 5-chlorothieno[2,3-c]pyridine (685 mg, 4.00 mmol), benzophenone imine (1.03 mL, 6.00 mmol), sodium tert-butoxide (595 mg, 6.00 mmol), Xantphos (358 mg, 0.600 mmol), tris(dibenzylideneacetone)dipalladium(0) (185 mg, 0.200 mmol) and toluene (40 mL) was heated at 120° C. under a nitrogen atmosphere for 3 h. After cooling, the reaction mixture was partitioned between EtOAc (50 mL) and water (50 mL). The aqueous layer was extracted with EtOAc (50 mL). The combined organic fractions were washed with water (30 mL) and brine (30 mL), dried over MgSO4, and concentrated in vacuo. The residue was dissolved in THF (80 mL) and treated with aqueous 2 N hydrochloric acid (8.0 mL, 16 mmol). After 1 h at RT, the reaction mixture was diluted with water (50 mL) and extracted with EtOAc (3×30 mL). The extracts were washed with water (2×30 mL) and brine (30 mL). The aqueous layer was treated with aqueous NaOH until the pH was >9 and then extracted with EtOAc (3×50 mL). The combined organic extracts were washed with brine (30 mL), dried over MgSO4, and concentrated in vacuo. The resultant solid was purified by ISCO chromatography (50% to 100% EtOAc:heptane) to afford 420 mg (70%) of the title compound as a yellow solid. 1H NMR (400 MHz, CDCl3) δ 8.64 (s, 1 H), 7.59 (d, J=5.6 Hz, 1 H), 7.12 (d, J=5.6 Hz, 1 H), 6.88 (d, J=1.2 Hz, 1 H), 4.36 (br s, 2 H); MS (ESI): 151.03 [M+H]+; HPLC tR=0.43 min (TOF: polar—3 min).

1. temperatureAfter cooling
2. customthe reaction mixture was partitioned between EtOAc (50 mL) and water (50 mL)
3. extractionThe aqueous layer was extracted with EtOAc (50 mL)
4. washThe combined organic fractions were washed with water (30 mL) and brine (30 mL)
5. dry with materialdried over MgSO4
6. concentrationconcentrated in vacuo
7. dissolutionThe residue was dissolved in THF (80 mL)
8. extractionextracted with EtOAc (3×30 mL)
9. washThe extracts were washed with water (2×30 mL) and brine (30 mL)
10. additionThe aqueous layer was treated with aqueous NaOH until the pH was >9
11. extractionextracted with EtOAc (3×50 mL)
12. washThe combined organic extracts were washed with brine (30 mL)
13. dry with materialdried over MgSO4
14. concentrationconcentrated in vacuo
15. customThe resultant solid was purified by ISCO chromatography (50% to 100% EtOAc:heptane)

ORD record

ord-ce47573717b14ac185795a7b8557827c

Source dataset

uspto-grants-2013_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08378104B2