Hydrochloric Acid → HCID 50899057, compound

Temperature

50 °C

A mixture of EXAMPLE 17A (0.130 g, 0.265 mmol) and concentrated hydrochloric acid (0.15 mL) in ethanol (6 mL) was heated at 95° C. for 24 h. The mixture was concentrated and the residue treated with saturated aqueous sodium bicarbonate, sonicated, filtered, and washed with water. The intermediate was suspended in dioxane (3.5 mL), treated with 20% sodium hydroxide (0.3 mL) and heated at 50° C. for 2 h. After concentration, the residue was treated with 6 mL of water. The solid was filtered, washed with water, and purified by reversed-phase HPLC (Zorbax RX-C18 column (250×21.2 mm, 7 μm particle size) using a gradient of 10% to 100% acetonitrile: 0.1% aqueous trifluoroacetic acid over 40 min at a flow rate of 15 mL/minute). The filtrate was also separately purified by HPLC to obtain a combined 46.5 mg (49%) of the title compound as the trifluoroacetate salt. 1H NMR (500 MHz, DMSO-d6) 7.28 (s, 1H), 7.47 (s, 1H), 8.34 (d, J=2.4 Hz, 1H), 8.52 (d, J=2.8 Hz, 1H), 8.58 (d, J=3.1 Hz, 1H), 12.55 (s, 1H). MS (ESI) m/z 246.3 (M+H)+.

1. concentrationThe mixture was concentrated
2. additionthe residue treated with saturated aqueous sodium bicarbonate
3. customsonicated
4. filtrationfiltered
5. washwashed with water
6. additiontreated with 20% sodium hydroxide (0.3 mL)
7. concentrationAfter concentration
8. additionthe residue was treated with 6 mL of water
9. filtrationThe solid was filtered
10. washwashed with water
11. custompurified by reversed-phase HPLC (Zorbax RX-C18 column (250×21.2 mm, 7 μm particle size)
12. customThe filtrate was also separately purified by HPLC

ORD record

ord-ef01ae9a53f44153a28f05efc7ce0421

Source dataset

uspto-grants-2013_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08383624B2