Methanol → 4-[[N-(2-amino-4,5-difluorobenzoyl)glycyl]aminomethyl]-1-(benzo[c]furazan-5-yl)piperidine

A mixture of 4-[[N-(2-(tert-butoxycarbonylamino)-4,5-difluorobenzoyl)glycyl]aminomethyl]piperidine (0.050 mmol) with 5-(bromomethyl)benzo[c]furazan (0.75 mL), a (piperidinomethyl)polystyrene (2.6-2.8 mmol/g, 60 mg, 0.15 mmol), methanol (0.2 mL), acetonitrile (1.0 mL) and chloroform (0.50 mL) was stirred at 50° C. overnight, cooled to room temperature, loaded onto a Varian™ SCX column and washed with methanol (5 mL×2). The obtained crude product was eluted with a 2 M methanol solution of NH3 (5 mL) and concentrated. Chloroform (1.5 mL) and phenyl isocyanate (0.075 mL) were added to the residue, and the resulting mixture was stirred at room temperature for 1 hour, loaded onto a Varian™ SCX column and washed with methanol (5 mLX 2). The obtained crude product was eluted with a 2 M methanol solution of NH3 (5 mL) and concentrated. The resulting residue was dissolved in methanol (1 mL), and a 4 M dioxane solution of HCl (0.50 ml) was added to the obtained solution. The resulting mixture was stirred at room temperature overnight and concentrated. The residue was then dissolved in methanol, loaded onto a Varian™ SCX column, washed with methanol (5 mL×2), eluted with a 2 M methanol solution of NH3 (5 mL), concentrated and then purified by preparative TLC (SiO2, ethyl acetate/methanol=5:1) to provide 4-[[N-(2-amino-4,5-difluorobenzoyl)glycyl]aminomethyl]-1-(benzo[c]furazan-5-yl)piperidine (Compd. No. 2130) (3.6 mg, 16%). The purity was determined by RPLC/MS (87%). ESI/MS m/e 459.3 (M++H, C22H24F2N6O3).

1. washwashed with methanol (5 mL×2)
2. customThe obtained crude product
3. washwas eluted with a 2 M methanol solution of NH3 (5 mL)
4. concentrationconcentrated
5. additionChloroform (1.5 mL) and phenyl isocyanate (0.075 mL) were added to the residue
6. washwashed with methanol (5 mLX 2)
7. customThe obtained crude product
8. washwas eluted with a 2 M methanol solution of NH3 (5 mL)
9. concentrationconcentrated
10. dissolutionThe resulting residue was dissolved in methanol (1 mL)
11. additiona 4 M dioxane solution of HCl (0.50 ml) was added to the obtained solution
12. stirringThe resulting mixture was stirred at room temperature overnight
13. concentrationconcentrated
14. dissolutionThe residue was then dissolved in methanol
15. washwashed with methanol (5 mL×2)
16. washeluted with a 2 M methanol solution of NH3 (5 mL)
17. concentrationconcentrated
18. custompurified by preparative TLC (SiO2, ethyl acetate/methanol=5:1)

ORD record

ord-5b3302665e2c4ebfba48b670de53180f

Source dataset

uspto-grants-2008_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07390830B1