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 acetatehexane 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 acetatehexane gradient
9. customThe product was collected
10. concentrationconcentrated in vacuo

ORD record

ord-0a8647af632a4de9a3001880b603454c

Source dataset

uspto-grants-2015_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09045496B2