HCID 45257321, Verbindung → (R,Z)-2-amino-7-(2-bromo-4-fluorophenyl)-4-methyl-7,8-dihydropyrido[4,3-d]pyrimidin-5(6H)-one O-2-((S)-2,2-dimethyl-1,3-dioxolan-4-yl)ethyl oxime

HRID 656584Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 656584
[NH2:1][C:2]1[N:3]=[C:4]([CH3:21])[C:5]2[C:11](=S)[NH:10][C@@H:9]([C:13]3[CH:18]=[CH:17][C:16]([F:19])=[CH:15][C:14]=3[Br:20])[CH2:8][C:6]=2[N:7]=1.[CH3:22][C:23]1([CH3:32])[O:27][C@@H:26]([CH2:28][CH2:29][O:30][NH2:31])[CH2:25][O:24]1>[Hg](OC(C)=O)OC(C)=O.C1(C)C=CC=CC=1>[CH3:22][C:23]1([CH3:32])[O:27][C@@H:26]([CH2:28][CH2:29][O:30]/[N:31]=[C:11]2\[NH:10][C@@H:9]([C:13]3[CH:18]=[CH:17][C:16]([F:19])=[CH:15][C:14]=3[Br:20])[CH2:8][C:6]3[N:7]=[C:2]([NH2:1])[N:3]=[C:4]([CH3:21])[C:5]\2=3)[CH2:25][O:24]1

Komponenten

5

Edukt 2

HCID 45257321HCID 45257321, VerbindungHCID 57999036(S)-O-(2-(2,2-dimethyl-1,3-dioxolan-4-yl)ethyl)hydroxylamine

Produkt 1

HCID 178433346(R,Z)-2-amino-7-(2-bromo-4-fluorophenyl)-4-methyl-7,8-dihydropyrido[4,3-d]pyrimidin-5(6H)-one O-2-((S)-2,2-dimethyl-1,3-dioxolan-4-yl)ethyl oximeAusbeute 65 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 16683746DiacetyloxymercuryKatalysatorHCID 1140TolueneLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

A mixture of (R)-2-amino-7-(2-bromo-4-fluorophenyl)-4-methyl-7,8-dihydropyrido[4,3-d]pyrimidine-5(6H)-thione (31I, 100 mg, 0.3 mmol), (S)—O-(2-(2,2-dimethyl-1,3-dioxolan-4-yl)ethyl)hydroxylamine (194 mg, 1.2 mmol), Hg(OAc)2 (192 mg, 0.6 mmol) and anhydrous toluene (2 mL) was heated at 100° C. for 1 h. LCMS shows completion of the reaction. The mixture was cooled, filtered through celite and washed with ethyl acetate. Filtrate concentrated and the resulting oily residue was purified by preparative LCMS to afford (R,Z)-2-amino-7-(2-bromo-4-fluorophenyl)-4-methyl-7,8-dihydropyrido[4,3-d]pyrimidin-5(6H)-one O-2-((S)-2,2-dimethyl-1,3-dioxolan-4-yl)ethyl oxime (35A, 87 mg, 65%) as a pale yellow solid. 1H NMR (400 MHz, CHLOROFORM-d) δ 1.35 (s, 3H) 1.40 (s, 3H) 2.01 (qd, J=6.32, 3.03 Hz, 2H) 2.76 (s, 3H) 2.95 (dd, J=16.42, 8.84 Hz, 1H) 3.18 (dd, J=17.18, 5.05 Hz, 1H) 3.56-3.62 (m, 1H) 4.09 (dd, J=7.96, 5.94 Hz, 1H) 4.16-4.28 (m, 2H) 4.98 (ddd, J=8.78, 4.61, 1.52 Hz, 1H) 7.07 (td, J=8.21, 2.53 Hz, 1H) 7.34 (dd, J=8.08, 2.53 Hz, 1H) 7.68 (dd, J=12.00, 6.95 Hz, 1H). MS (ES) [M+H] calculated for C21H26BrFN5O3, 494.11. found 494.00.

Aufarbeitung

  1. customcompletion of the reaction
  2. temperatureThe mixture was cooled
  3. filtrationfiltered through celite
  4. washwashed with ethyl acetate
  5. concentrationFiltrate concentrated
  6. customthe resulting oily residue was purified by preparative LCMS

Quellen und Nachweise

ORD-Eintrag
ord-4a70a9fa8ae54da1996ba47653e5fd79
Quelldatensatz
uspto-grants-2011_12
Patentnummer
US08071766B2

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