Hydrochloric Acid → 1-(3-Bromo-4-fluorophenyl)-4-fluoro-1-(pyridin-4-yl)-1H-isoindol-3-amine

Temperature

-100 °C

A solution of 4-iodopyridine (0.530 g, 2.59 mmol) in THF (5 mL) was added dropwise to a is mixture of tert-butyllithium (1.6 M in pentane, 2.94 mL, 4.70 mmol) in THF (20.00 mL) at −100° C. under an argon atmosphere. N-((3-Bromo-4-fluorophenyl)(2-cyano-3-fluorophenyl)methylene)-2-methylpropane-2-sulfinamide (1.00 g, 2.35 mmol) in THF (7.50 mL) was added and the resulting reaction mixture was stirred at −100° C. for 30 min. The cooling bath was removed and the mixture was stirred at room temperature for 2 h. Water was added and the mixture was extracted with EtOAc (×3). The combined organic layers were dried over Na2SO4 and concentrated. The residue was dissolved in MeOH (15.00 mL), and then hydrogen chloride (2 M in diethyl ether, 2.351 mL, 4.70 mmol) was added and the mixture was stirred at room temperature for 1.5 h. The solvents were removed in vacuo, and the residue was partitioned between aqueous sodium bicarbonate (saturated) and chloroform. The combined organic layers were dried (Na2SO4), filtered and concentrated in vacuo. Purification by silica gel chromatography using a gradient of 0 to 10% (3.5 M ammonia in methanol) in dichloromethane afforded 0.088 g (9% yield) of the title compound. MS (ES+) m/z 400 [M+1]+.

1. customthe resulting reaction mixture
2. customThe cooling bath was removed
3. stirringthe mixture was stirred at room temperature for 2 h
4. additionWater was added
5. extractionthe mixture was extracted with EtOAc (×3)
6. dry with materialThe combined organic layers were dried over Na2SO4
7. concentrationconcentrated
8. dissolutionThe residue was dissolved in MeOH (15.00 mL)
9. stirringthe mixture was stirred at room temperature for 1.5 h
10. customThe solvents were removed in vacuo
11. customthe residue was partitioned between aqueous sodium bicarbonate (saturated) and chloroform
12. dry with materialThe combined organic layers were dried (Na2SO4)
13. filtrationfiltered
14. concentrationconcentrated in vacuo
15. customPurification by silica gel chromatography

ORD record

ord-f698187867bd442cae07cbe01d31ef25

Source dataset

uspto-grants-2011_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08030500B2