Hydrochloric Acid → 2-Chloro-9-cyclopentyl-7-fluoro-7-methyl-8,9-dihydro-5H-pyrimido[4,5-b][1,4]diazepin-6(7H)-one

HRID 1880917Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1880917
[Cl:1][C:2]1[N:7]=[C:6]([N:8]([CH:18]2[CH2:22][CH2:21][CH2:20][CH2:19]2)[CH2:9][C:10]([F:17])([CH3:16])[C:11](OCC)=[O:12])[C:5]([N+:23]([O-])=O)=[CH:4][N:3]=1.Cl>C(O)(=O)C>[Cl:1][C:2]1[N:3]=[CH:4][C:5]2[NH:23][C:11](=[O:12])[C:10]([F:17])([CH3:16])[CH2:9][N:8]([CH:18]3[CH2:22][CH2:21][CH2:20][CH2:19]3)[C:6]=2[N:7]=1

Komponenten

4

Edukt 2

HCID 313Hydrochloric AcidHCID 57955550Ethyl 3-((2-chloro-5-nitropyrimidin-4-yl)(cyclopentyl)amino)-2-fluoro-2-methylpropanoate

Produkt 1

HCID 579556652-Chloro-9-cyclopentyl-7-fluoro-7-methyl-8,9-dihydro-5H-pyrimido[4,5-b][1,4]diazepin-6(7H)-oneAusbeute 23,1 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 176Acetic AcidLösungsmittel

Reaktionsbedingungen

Temperatur
60 °C

Versuchsvorschrift

To a suspension of ethyl 3-((2-chloro-5-nitropyrimidin-4-yl)(cyclopentyl)amino)-2-fluoro-2-methylpropanoate (3.4 g, 9 mmol), reduced iron (1.2 g, 23 mmol) in acetic acid (20 ml) was added dropwise concentrated hydrochloric acid (2 ml) at 0° C. The reaction mixture was stirred at 60° C. for 18 h. It was then concentrated in vacuo, diluted to 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 product (620 mg, 23% yield) as white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.42-1.67 (m, 7 H) 1.72 (d, J=4.0 Hz, 2 H) 1.77-1.91 (m, 2 H) 3.58-3.77 (m, 2 H) 5.01 (t, J=8.2 Hz, 1 H) 7.97 (s, 1 H) 10.36 (s, 1 H). [M+H] calc'd for C13H16ClFN4O, 299; found 299.

Aufarbeitung

  1. concentrationIt was then concentrated in vacuo
  2. additiondiluted to EtOAc
  3. custombasified with 10% NaOH solution at 0° C
  4. filtrationThe whole was filtered through celite
  5. washwashed with EtOAc
  6. customThe filtrate was then separated
  7. dry with materialThe organic layer was dried over Na2SO4
  8. concentrationThe solution was concentrated in vacuo
  9. customfollowed by precipitation from ether

Quellen und Nachweise

ORD-Eintrag
ord-282cf768c7484f2192e91e566002603c
Quelldatensatz
uspto-grants-2012_11
Patentnummer
US08318727B2

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