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 1881016

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, 6 H) 3.42 (s, 3 H) 3.89 (t, J=12.38 Hz, 2 H) 4.97-5.10 (m, 1 H) 8.06 (s, 1 H).

Workup

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

Sources & evidence

ORD record: ord-363da73a19e04e2b90ebb4c650393298
Source dataset: uspto-grants-2012_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08318727B2

Linked notes

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