Chloroform → HCID 178506015, compound

Temperature

0 °C

To a stirred solution of 6-chloro-2-fluoropurine (0.4 g, 1 eq, 2.31 mmol) in n-BuOH (25 mL) under an argon atmosphere, cooled to 0° C., was added DIEA (1.13 mL, 2.80 eq, 6.49 mmol) followed by C-pyridin-2-yl-methylamine (0.48 mL, 2.0 eq, 4.66 mmol). The reaction mixture was stirred at 0° C. for 3 h, and then allowed to return to room temperature over 30 min. and stirred at this temperature for 1 h, when TLC (CHCl3:MeOH; 90:10) indicated that the reaction had gone to completion. The solvent was evaporated in vacuo and the residue partitioned between citric acid solution (200 mL, 10% aq.) and EtOAc (200 mL), the aqueous phase was separated and extracted with more EtOAc (2×100 mL), and the bulked organic phase containing traces of 6-chloro-2-fluoropurine was discarded. The pH of the aqueous phase was adjusted to 7.0 with NaOH solution (50% w/v, aq.), extracted with EtOAc (4×100 mL), and the bulked organic phase was washed with brine (50 mL), dried (MgSO4) and evaporated in vacuo. The residue was purified by gradient column chromatography on silica gel, eluted with CHCl3:MeOH (95:5→85:15), to afford the title compound as a light yellow solid. Yield: 0.40 g (71%). Mp 217-220° C. 1H-NMR (d6-DMSO, 250 MHz): δ4.58 (d, 2H, J=5.68 Hz, —HNCH2-Pyr), 7.29, 7.71, 8.49 (3×m, 4H, Pyr), 8.10 (s, 1H, —N═CH—NH—), 8.69 (bs, 1H, —HNCH2-Pyr), 13.07 (bs, 1H, —N═CH—NH13 ). FABMS m/z (relative intensity): 245 ([M+H]+, 55), 176 (30), 154 (100), 136 (85). Accurate Mass (M+H): Actual: 245.0951, Measured: 245.0942. Microanalysis (Expected: Measured) C11H9N6F .0.4H20: C; 52.55: 52.91, H; 3.93: 3.49, N; 33.42: 33.26.

1. waitto return to room temperature over 30 min.
2. stirringstirred at this temperature for 1 h
3. customThe solvent was evaporated in vacuo
4. customthe residue partitioned between citric acid solution (200 mL, 10% aq.) and EtOAc (200 mL)
5. customthe aqueous phase was separated
6. extractionextracted with more EtOAc (2×100 mL)
7. additionthe bulked organic phase containing traces of 6-chloro-2-fluoropurine
8. extractionextracted with EtOAc (4×100 mL)
9. washthe bulked organic phase was washed with brine (50 mL)
10. dry with materialdried (MgSO4)
11. customevaporated in vacuo
12. customThe residue was purified by gradient column chromatography on silica gel
13. washeluted with CHCl3:MeOH (95:5→85:15)

ORD record

ord-a9a08f63314a4ed5a7e9dc47fad44566

Source dataset

uspto-grants-2009_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07544689B2