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

반응식

HRID 1881016 반응식
[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

참가 물질

6

반응물 1

HCID 86635898Ethyl 3-((2-chloro-5-nitropyrimidin-4-yl)(isopropyl)amino)-2,2-difluoropropanoate

생성물 1

HCID 866358992-chloro-7,7-difluoro-9-isopropyl-8,9-dihydro-5H-pyrimido[4,5-b][1,4]diazepin-6(7H)-one수율 54.2%

시약·촉매·용매 4

HCID 23925Iron촉매HCID 176Acetic Acid용매HCID 313Hydrochloric Acid용매HCID 962Water용매

반응 조건

온도
60 °C

실험 절차

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).

후처리

  1. extractionextracted with ethyl acetate
  2. customThe combined organic extracts were dried
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified

출처 및 근거

ORD 기록
ord-363da73a19e04e2b90ebb4c650393298
출처 데이터셋
uspto-grants-2012_11
특허 번호
US08318727B2

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