Bromomethylcyclopropane → 2-Chloro-5-(cyclopropylmethyl)-5,6,6a,7,9,10-hexahydro-[1,4]oxazino[3,4-h]pteridine

2-Chloro-5,6,6a,7,9,10-hexahydro-[1,4]oxazino[3,4-h]pteridine (PREPARATION x2, 200 mg, 0.882 mmol) was dissolved in DMSO (4.4 mL). Sodium tert-butoxide (102 mg, 1.059 mmol) was then added to give a brown solution. After 5 minutes, (bromomethyl)cyclopropane (86 μL, 0.882 mmol) was added dropwise. The reaction mixture was stirred for 2 hours at room temperature then quenched with aqueous saturated NH4Cl. The reaction mixture was diluted with ethyl acetate and washed with aqueous saturated NH4Cl (3×25 mL). The combined organic layers were dried over MgSO4, filtered, and concentrated in vacuo. The crude product was loaded onto an ISCO® silica gel cartridge (12 g) and eluted with an ethyl acetate/hexane gradient. The product was collected and concentrated in vacuo to afford the title compound as a yellow oil (100 mg, 40%). ESI-MS m/z [M+H]+ calc'd for C13H17ClN4O, 281.1. found 281.3.

1. customto give a brown solution
2. customthen quenched with aqueous saturated NH4Cl
3. additionThe reaction mixture was diluted with ethyl acetate
4. washwashed with aqueous saturated NH4Cl (3×25 mL)
5. dry with materialThe combined organic layers were dried over MgSO4
6. filtrationfiltered
7. concentrationconcentrated in vacuo
8. washeluted with an ethyl acetate/hexane gradient
9. customThe product was collected
10. concentrationconcentrated in vacuo

ORD record

ord-55b28992366d48749a45ecf1d9c54e1c

Source dataset

uspto-grants-2014_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08791107B2