Hydrochloric Acid → 2-(1-(2-Fluoro-4-(6-(3-(3-(trifluoromethyl)phenyl)ureido)pyridin-3-yl)phenyl)cyclobutoxy)acetic acid

温度

90 °C

A 25 mL vial was charged with the product from Example 60C (459 mg, 1.128 mmol), the product from Example 60B (342 mg, 1.128 mmol), dibasic potassium phosphate (590 mg, 3.38 mmol), and 1,1′-bis(di-tert-butylphosphino)ferrocene palladium (II) dichloride (7.38 mg, 0.011 mmol), N,N-dimethylacetamide (4 mL), ethanol (4.00 ml) and water (2 mL). The suspension was stirred and heated to 90° C., whereupon the reaction became homogenous. After heating at 90° C. for 1 hour; the reaction was cooled to room temperature. The resulting suspension was poured into water (200 mL). The mixture was acidified to pH 1 with 1 M HCl. The solid was filtered, washed with water, and air-dried to give the title product. 1H NMR (300 MHz, DMSO-d6) δ ppm 1.62-1.71 (m, 1 H), 1.96-2.07 (m, 1 H), 2.39-2.49 (m, 4 H), 3.69 (s, 2 H), 7.38 (d, J=7.12Hz, 1 H), 7.47-7.61 (m, 4 H), 7.65-7.71 (m, 2 H), 8.07 (s, 1 H), 8.17 (dd, J=2.7 and 8.8 Hz, 1 H), 8.71 (d, J=2.7 Hz, 1 H), 9.68 (s, 1 H), 10.65 (s, 1 H), 12.5 (br s, 1 H). MS (ESI) m/z 504 [M+H]+.

1. temperatureAfter heating at 90° C. for 1 hour
2. temperaturethe reaction was cooled to room temperature
3. filtrationThe solid was filtered
4. washwashed with water
5. customair-dried

ORDレコード

ord-2d4ed0e6d2fb40bf82b2f6daf105acb1

出典データセット

uspto-grants-2014_12

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08901152B2