N-Iodosuccinimide → HCID 86650629, compound

Temperature

0 °C

6-chloro-N-((tetrahydro-2H-pyran-4-yl)methyl)pyrazin-2-amine (0.250 g, 1.098 mmol) was dissolved in a mixture of DMSO (4.30 ml) and H2O (0.105 ml). It was cooled to 0° C. in an ice bath and was then treated with N-iodosuccinimide (0.247 g, 1.098 mmol) by portion-wise addition. Once the addition was complete the reaction mixture was stirred at ambient temperature for 24 hr. Additional NIS (0.025 g, 0.111 mmol) was added. Stirring at ambient temperature was continued for 24 hr. The reaction mixture was diluted with H2O (50 ml). This was extracted with EtOAc (3×50 ml). The organic layers were combined and washed with brine (1×50 ml). The organic layer was dried (Na2SO4), filtered, and the solvent removed in vacuo to give 0.410 g of crude product. The resulting residue was subjected to silica gel column chromatography. Elution using 30 EtOAc/70 heptane to 100 EtOAc gave 0.2144 g (55%) of 6-chloro-5-iodo-N-((tetrahydro-2H-pyran-4-yl)methyl)pyrazin-2-amine. LCMS (m/z): 353.9 (MH+), retention time=0.92 min. 1H NMR (400 MHz, CHLOROFORM-d) d ppm 1.37 (qd, 2H) 1.59 (s, 2H) 1.67 (d, J=12.91 Hz, 2H) 1.77-1.94 (m, J=14.87, 7.63, 7.63, 3.52 Hz, 1H) 3.25 (t, J=6.46 Hz, 2H) 3.39 (td, J=11.74, 1.96 Hz, 2H) 4.00 (dd, J=11.15, 3.72 Hz, 2H) 4.80 (br. s., 1H) 7.62 (s, 1H).

1. additionOnce the addition
2. stirringStirring at ambient temperature
3. waitwas continued for 24 hr
4. extractionThis was extracted with EtOAc (3×50 ml)
5. washwashed with brine (1×50 ml)
6. dry with materialThe organic layer was dried (Na2SO4)
7. filtrationfiltered
8. customthe solvent removed in vacuo
9. customto give 0.410 g of crude product
10. washElution

ORD record

ord-f6f8dbc289ea4a089f71389e3852a4ad

Source dataset

uspto-grants-2014_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08778951B2