1-(3-Fluorobenzyl)-1H-indazol-5-amine → (3R,4R)-1-((4-(1-(3-fluorobenzyl)-1H-indazol-5-ylamino)quinazolin-5-yl)methyl)-4-azidopiperidin-3-ol

Temperature

55 °C

A mixture of 14A (120 mg, 0.34 mmol) and 1-(3-fluorobenzyl)-1H-indazole-5-amine (81.0 mg, 0.34 mmol; prepared as described in US 2003/0186983 A1) in CH3CN (1.2 ml) was heated at 55° C. for 45 min. After cooled to rt, (3R,4R)-4-azidopiperidin-3-ol (475 mg, 3.34 mmol; prepared as described in U.S. patent application Ser. No. 10146 PSP) was added and the mixture was heated at 60° C. for 16 h. This mixture was diluted with CH3CN (2.4 mL), and then heated at 70° C. for 4 h and at 80° C. for 4 d. The reaction mixture was concentrated in vacuo and the residue was purified by prep HPLC. to give 19A (78 mg, 45%). It has an analytical HPLC retention time=2.43 min (Chromolith SpeedROD column 4.6×50 mm, 10-90% aqueous methanol containing 0.2% H3PO4 over 4 minutes, 4 mL/min, monitoring at 220 nm) and a LC/MS M++H=524+.

1. temperatureAfter cooled to rt
2. customprepared
3. addition10146 PSP) was added
4. temperaturethe mixture was heated at 60° C. for 16 h
5. temperatureheated at 70° C. for 4 h and at 80° C. for 4 d
6. concentrationThe reaction mixture was concentrated in vacuo
7. customthe residue was purified by prep HPLC

ORD record

ord-22caf0361bc743709528d7a92502b449

Source dataset

uspto-grants-2008_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07358256B2