4-Toluenesulfonyl chloride → HCID 59160638, compound

To a magnetically stirred solution of 5-fluoro-2-(4-methylbenzyloxy)pyrimidin-4-amine (200 mg, 0.857 mmol) in sure seal THF (4 mL) was added 1M lithium bis(trimethylsilyl)amide (LiHMDS) solution in THF (1.28 mL, 1.28 mmol) causing a slight exotherm. After stirring for 5 min, p-toluenesulfonyl chloride (196.65 mg, 1.028 mmol) was added and after 10 min the orange solution turned light yellow and turbid. The mixture was stirred at room temperature for 4 h. The solvent was removed in vacuo and the resulting viscous gold oil was diluted in EtOAc (50 mL), poured into a separatory funnel containing EtOAc (75 mL) and washed with 1N HCl aqueous solution (4×75 mL) followed by brine solution (1×100 mL). The organic extract was dried over Na2SO4, filtered, and evaporated. To the crude oil material was added distilled water (150 mL) and the resulting mixture was vigorously stirred at room temperature over 72 h forming an off-white solid. The solid was collected by vacuum filtration and air dried for 1 hour followed by drying under vacuum for 24 hours. The white solid was then suspended in Et2O (2 mL) for 1 h, then collected by vacuum filtration washed with Et2O (1×1 mL), and air dried for 1 h to yield N-(5-fluoro-2-(4-methylbenzyloxy)pyrimidin-4-yl)-4-methylbenzenesulfonamide (150 mg, 45.2% yield) as a white solid: mp 120-122° C.; 1H NMR (300 MHz, DMSO-d6) δ 8.28 (d, J=2.9 Hz, 1H), 7.83 (d, J=8.1 Hz, 2H), 7.33 (d, J=8.0 Hz, 2H), 7.23 (d, J=8.23 Hz, 2H), 7.16 (d, J=7.92 Hz, 2H), 5.08 (s, 2H), 2.33 (s, 3H), 2.29 (s, 3H) MS (ESI) m/z 386.3 (M−H)−.

1. stirringThe mixture was stirred at room temperature for 4 h
2. customThe solvent was removed in vacuo
3. additionthe resulting viscous gold oil was diluted in EtOAc (50 mL)
4. additionpoured into a separatory funnel
5. additioncontaining EtOAc (75 mL)
6. washwashed with 1N HCl aqueous solution (4×75 mL)
7. extractionThe organic extract
8. dry with materialwas dried over Na2SO4
9. filtrationfiltered
10. customevaporated
11. additionTo the crude oil material was added
12. distillationdistilled water (150 mL)
13. stirringthe resulting mixture was vigorously stirred at room temperature over 72 h
14. customforming an off-white solid
15. filtrationThe solid was collected by vacuum filtration and air
16. customdried for 1 hour
17. customby drying under vacuum for 24 hours
18. waitThe white solid was then suspended in Et2O (2 mL) for 1 h
19. filtrationcollected by vacuum filtration
20. washwashed with Et2O (1×1 mL), and air
21. customdried for 1 h

ORD record

ord-69e7a35d28ef4a83b2382aa5a718f52b

Source dataset

uspto-grants-2015_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09204653B2