Morpholine → N-(3-(4-fluorophenyl)-1-(2-morpholinoethyl)-4-(phenylethynyl)-1H-pyrazol-5-yl)acetamide

To a suspension of N-(3-(4-fluorophenyl)-1-(2-hydroxyethyl)-4-(phenylethynyl)-1H-pyrazol-5-yl)acetamide (269 mg, 0.74 mmol) in CH2Cl2 (9 mL) and triethylamine (155 μl, 1.11 mmol) was added methanesulphonyl chloride (65 μl, 0.81 mmol and the reaction stirred at room temperature for 16 h. The reaction mixture was poured onto ice/water and the organic layer was dried over MgSO4, filtered and evaporated. The crude product was dissolved in THF (10 ml) and morpholine (320 μl, 3.7 mmol) was added. The reaction was heated to 55° C. for 24 h before evaporating the solvent in vacuo. The crude was partitioned between CH2Cl2 and dilute aqueous NaHCO3 and the organic layer was dried over MgSO4, filtered and evaporated. Purification using chromatography (silica gel, gradient 0 to 10% methanol/CH2Cl2) gave N-(3-(4-fluorophenyl)-1-(2-morpholinoethyl)-4-(phenylethynyl)-1H-pyrazol-5-yl)acetamide as a white solid (141 mg) which was used as such in the subsequent step.

1. additionThe reaction mixture was poured onto ice/water
2. dry with materialthe organic layer was dried over MgSO4
3. filtrationfiltered
4. customevaporated
5. dissolutionThe crude product was dissolved in THF (10 ml)
6. temperatureThe reaction was heated to 55° C. for 24 h
7. custombefore evaporating the solvent in vacuo
8. customThe crude was partitioned between CH2Cl2 and dilute aqueous NaHCO3
9. dry with materialthe organic layer was dried over MgSO4
10. filtrationfiltered
11. customevaporated
12. customPurification

ORD record

ord-815f5c1207d74cb39e4a1eefba078071

Source dataset

uspto-grants-2015_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09079909B2