Hydrochloric Acid → 2-Chloro-9-cyclohexyl-7,7-difluoro-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-one

Temperature

0 °C

In a round bottom flask compound ethyl 4-((2-chloro-5-nitropyrimidin-4-yl)(cyclohexyl)amino)-3,3-difluoro-2-oxobutanoate (11.85 g, 31.35 mmol) was dissolved in acetic acid (30 mL), and added iron powder (3.51 g, 62.7 mmol) to it. Then cooled the round bottom flask to 0° C. in an ice bath. After 10 min, added conc.HCl (12 mL) dropwise using addition funnel and continued the reaction at 60° C. on a preheated oil bath until starting material disappear. It was then concentrated in vacuo, diluted with EtOAc, basified with 10% NaOH solution at 0° C. The whole was filtered through celite, washed with EtOAc. The filtrate was then separated. The organic layer was dried over Na2SO4. The solution was concentrated in vacuo followed by precipitation from ether to afford the desired compound (6.0 g, 62% yield) as yellow solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 0.96-1.85 (m, 10 H) 4.02 (t, J=11.37 Hz, 2 H) 4.47 (m, 1 H) 8.11 (s, 1 H) 11.02 (br. s., 1 H). [M+H] calc'd for C13H15ClF2N4O, 317; found 317.

1. additionadded conc
2. additionaddition funnel
3. customthe reaction at 60° C. on a preheated oil bath
4. concentrationIt was then concentrated in vacuo
5. additiondiluted with EtOAc
6. custombasified with 10% NaOH solution at 0° C
7. filtrationThe whole was filtered through celite
8. washwashed with EtOAc
9. customThe filtrate was then separated
10. dry with materialThe organic layer was dried over Na2SO4
11. concentrationThe solution was concentrated in vacuo
12. customfollowed by precipitation from ether

ORD record

ord-4abee2ecd680458587effee7626e2112

Source dataset

uspto-grants-2012_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08318727B2