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. The resulting aq mixture was basified with aq NaOH (2.0 M) and was then extracted with DCM (2×30 mL). The combined organic extracts were dried and evaporated in vacuo to afford the title compound, Intermediate A13, 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. extractionwas then extracted with DCM (2×30 mL)
12. customThe combined organic extracts were dried
13. customevaporated in vacuo

ORD record

ord-6f3b6e8b61794fdf8dcfa2ea3382f3df

Source dataset

uspto-grants-2015_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08933228B2