2-Methoxyethylamine → 1-(4-Fluorophenyl)-1H-pyrazolo[3,4-c]pyridine-4-carboxylic acid[6-(2-methoxy-ethylsulfamoyl)-pyridin-3-ylmethyl]-amide

To a solution of 3-[5-({[1-(4-fluorophenyl)-1H-pyrazolo[3,4-c]pyridine-4-carbonyl]-amino}-methyl)-pyridine-2-sulfonyl]-propionic acid methyl ester (100 mg, 0.2 mmol) in THF (5 mL) was added a freshly prepared 8% solution of sodium ethoxide (200 μL, 0.2 mmol) in ethanol. The mixture was stirred for 15 minutes and was monitored for the disappearance of starting material by TLC (EtOAc). The mixture was then concentrated to dryness under a stream of nitrogen. The mixture was again diluted with THF and then N-chlorosuccinimide (55 mg, 0.41 mmol) was added. After 15 minutes, 2-methoxyethylamine (0.100 mL, 1.15 mmol) was added in one portion. After 15 minutes, the mixture was diluted with saturated ammonium chloride and extracted with EtOAc (3×10 mL). The combined organic layers were washed with brine (2×10 mL), dried over magnesium sulfate, filtered and concentrated. The crude material was purified by silica gel chromatography eluting with methanol-EtOAc (0:100, then 0.5:99.5, then 1:99, then 2:98). The material from the column was purified a second time by using preparative silica gel TLC eluting with methanol-EtOAc (1:9). The material from the plate was triturated with EtOAc-ether-hexanes to afford the title compound.

1. concentrationThe mixture was then concentrated to dryness under a stream of nitrogen
2. additionThe mixture was again diluted with THF
3. waitAfter 15 minutes
4. waitAfter 15 minutes
5. extractionextracted with EtOAc (3×10 mL)
6. washThe combined organic layers were washed with brine (2×10 mL)
7. dry with materialdried over magnesium sulfate
8. filtrationfiltered
9. concentrationconcentrated
10. customThe crude material was purified by silica gel chromatography
11. washeluting with methanol-EtOAc (0:100
12. customThe material from the column was purified a second time
13. washeluting with methanol-EtOAc (1:9)
14. customThe material from the plate was triturated with EtOAc-ether-hexanes

ORDレコード

ord-232218545b994e689bf694f218bd2ee7

出典データセット

uspto-grants-2012_12

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08338610B2