Cesium carbonate → 9-(4-cyclopropylpiperazin-1-yl)-6-(4-methoxybenzyl)pyrido[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one

HRID 926114

Reaktionsgleichung

Reaktionsgleichung von HRID 926114
Br[C:2]1[CH:11]=[N:10][C:9]2[N:8]([CH2:12][C:13]3[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][CH:14]=3)[C:7](=[O:21])[N:6]3[N:22]=[CH:23][N:24]=[C:5]3[C:4]=2[CH:3]=1.[CH:25]1([N:28]2[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]2)[CH2:27][CH2:26]1.C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.C([O-])([O-])=O.[Cs+].[Cs+]>C1(C)C=CC=CC=1.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH:25]1([N:28]2[CH2:33][CH2:32][N:31]([C:2]3[CH:11]=[N:10][C:9]4[N:8]([CH2:12][C:13]5[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][CH:14]=5)[C:7](=[O:21])[N:6]5[N:22]=[CH:23][N:24]=[C:5]5[C:4]=4[CH:3]=3)[CH2:30][CH2:29]2)[CH2:27][CH2:26]1

Komponenten

7

Edukt 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 47420041-CyclopropylpiperazineHCID 867053859-bromo-6-(4-methoxybenzyl)pyrido[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one

Produkt 1

HCID 867053889-(4-cyclopropylpiperazin-1-yl)-6-(4-methoxybenzyl)pyrido[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-oneAusbeute 36,2 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 167845palladium(II) acetateKatalysatorHCID 1140TolueneLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

9-Bromo-6-(4-methoxybenzyl)pyrido[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one (Example 1, 63 mg, 0.16 mmol) and 1-cyclopropylpiperazine (103 mg, 0.82 mmol) were dissolved in toluene (2 mL) and nitrogen was bubbled through the mixture while BINAP (41 mg, 0.07 mmol), Cs2CO3 (159 mg, 0.49 mmol) and Pd(OAc)2 (7 mg, 0.03 mmol) were added. The mixture was heated at 100° C. for 16 h. The reaction mixture was concentrated under a stream of nitrogen and the residue was taken up in DMF and filtered. Purification (preparative HPLC, 10-70% ACN in water) afforded the title compound (25 mg, 27%) as a yellow solid. 1H NMR (400 MHz, CDCl3) δ 0.84-1.00 (m, 2H), 1.38 (d, J=3.01 Hz, 2H), 2.01 (s, 2H), 2.35-2.51 (m, 1H), 3.50 (s, 4H), 3.61 (br s, 4H), 3.76 (s, 3H), 5.70 (s, 2H), 6.82 (d, J=8.53 Hz, 2H), 7.57 (d, J=8.41 Hz, 2H), 8.07 (d, J=2.89 Hz, 1H), 8.33 (s, 1H), 8.47 (d, J=2.89 Hz, 1H). [M+H]=432.2.

Aufarbeitung

  1. additionwere added
  2. concentrationThe reaction mixture was concentrated under a stream of nitrogen
  3. filtrationfiltered
  4. customPurification (preparative HPLC, 10-70% ACN in water)

Quellen und Nachweise

ORD-Eintrag
ord-83c8a21b0d114c889a9e44d629030d32
Quelldatensatz
uspto-grants-2016_03
Patentnummer
US09284335B2

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