Ethyl 3-((2-chloro-5-nitropyrimidin-4-yl)(isopropyl)amino)-2,2-difluoropropanoate → 2-chloro-7,7-difluoro-9-isopropyl-8,9-dihydro-5H-pyrimido[4,5-b][1,4]diazepin-6(7H)-one

HRID 914245

Reaction equation

[Cl:1][C:2]1[N:7]=[C:6]([N:8]([CH:18]([CH3:20])[CH3:19])[CH2:9][C:10]([F:17])([F:16])[C:11](OCC)=[O:12])[C:5]([N+:21]([O-])=O)=[CH:4][N:3]=1>CC(O)=O.Cl.O.[Fe]>[Cl:1][C:2]1[N:3]=[CH:4][C:5]2[NH:21][C:11](=[O:12])[C:10]([F:17])([F:16])[CH2:9][N:8]([CH:18]([CH3:20])[CH3:19])[C:6]=2[N:7]=1

Participants

Conditions

Temperature: 60 °C

Procedure

Ethyl 3-((2-chloro-5-nitropyrimidin-4-yl)(isopropyl)amino)-2,2-difluoropropanoate (1.90 g, 5.39 mmol) was dissolved in HOAc (10 mL) and HCl (conc, 3.1 mL). Iron (0.610 g, 10.9 mmol) was added and the rm was stirred at rt for 3 h and at 60° C. overnight. The mixture was diluted with water and extracted with ethyl acetate. The combined organic extracts were dried, filtered and concentrated in vacuo. The residue was purified using flash column chromatography on silica gel (40 g SiO2, hexanes:ethyl acetate 2:1-1:1) to afford the title compounds as a light yellow solid (0.809 g, 54%). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.27 (d, J=6.82 Hz, 6H) 3.42 (s, 3H) 3.89 (t, J=12.38 Hz, 2H) 4.97-5.10 (m, 1H) 8.06 (s, 1H).

Workup

extractionextracted with ethyl acetate
customThe combined organic extracts were dried
filtrationfiltered
concentrationconcentrated in vacuo
customThe residue was purified

Sources & evidence

ORD record: ord-af1e3438f72747a9bee8dc7c0ccb0a97
Source dataset: uspto-grants-2011_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08026234B2

Linked notes

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