Sodium Hydroxide → HCID 71253525, compound

Temperature

0 °C

To a suspension of 1-(4-aminophenyl)-N-methylmethanesulfonamide (500 mg, 2.50 mmol) in hydrochloric acid (6 M, 10 mL) at 0° C. was added a solution of sodium nitrite (181 mg, 2.62 mmol) in water (3.0 mL) over 5 min. The reaction mixture was maintained at 0° C. for 2.5 hr, was treated with tin(II) chloride (1.33 g, 6.99 mmol) in hydrochloric acid (6M, 15 mL) and was then warmed to RT for 64 hr. The resulting mixture was basified to pH 12 with aq NaOH (6.0 M) and was extracted with EtOAc (2×100 mL). The combined organic extracts were washed with water and then dried and evaporated in vacuo to give a residue that was suspended in ethanol (10 mL) and treated with 4,4-dimethyl-3-oxopentanenitrile (160 mg, 1.3 mmol) and conc hydrochloric acid (12 M, 106 μL, 1.27 mmol). The resulting mixture was heated at reflux for 5 hr and after a further 23 hr at RT was evaporated in vacuo, to remove the ethanol and the resulting aq mixture basified with aq NaOH (2.0 M) and then extracted with DCM (2×30 mL). The combined organic extracts were dried and evaporated in vacuo to afford the title compound, Intermediate A24, as an orange solid (146 mg, 85% purity, 15%); Rt 1.34 min (Method 2); m/z 323 (M+H)+, (ES+). This material was used in subsequent steps without further purification

1. temperaturewas then warmed to RT for 64 hr
2. extractionwas extracted with EtOAc (2×100 mL)
3. washThe combined organic extracts were washed with water
4. customdried
5. customevaporated in vacuo
6. customto give a residue that
7. temperatureThe resulting mixture was heated
8. temperatureat reflux for 5 hr and after a further 23 hr at RT
9. customwas evaporated in vacuo
10. customto remove the ethanol
11. extractionextracted with DCM (2×30 mL)
12. customThe combined organic extracts were dried
13. customevaporated in vacuo

ORD record

ord-ba31369334b34065ab2fee9f9435fd21

Source dataset

uspto-grants-2015_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09024041B2