Sodium Carbonate → Ethyl 4-amino-7-(3-fluorophenyl)-5-{4-[({[4-(trifluoromethyl)pyridin-2-yl]amino}carbonyl)amino]phenyl}-pyrrolo[2,1-f][1,2,4]triazine-6-carboxylate

HRID 1094882Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1094882
[C:1]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C[CH:2]=1.[NH2:20][C:21]1[C:26]2=[C:27]([C:34]3[CH:39]=[CH:38][C:37]([NH:40][C:41]([NH:43][C:44]4[CH:49]=[C:48]([C:50]([F:53])([F:52])[F:51])[CH:47]=[CH:46][N:45]=4)=[O:42])=[CH:36][CH:35]=3)[C:28]([C:31]([O-:33])=[O:32])=[C:29](Br)[N:25]2[N:24]=[CH:23][N:22]=1.[F:54][C:55]1[CH:56]=[C:57](B(O)O)[CH:58]=[CH:59][CH:60]=1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[NH2:20][C:21]1[C:26]2=[C:27]([C:34]3[CH:39]=[CH:38][C:37]([NH:40][C:41]([NH:43][C:44]4[CH:49]=[C:48]([C:50]([F:53])([F:52])[F:51])[CH:47]=[CH:46][N:45]=4)=[O:42])=[CH:36][CH:35]=3)[C:28]([C:31]([O:33][CH2:1][CH3:2])=[O:32])=[C:29]([C:59]3[CH:58]=[CH:57][CH:56]=[C:55]([F:54])[CH:60]=3)[N:25]2[N:24]=[CH:23][N:22]=1

Komponenten

7

Edukt 4

HCID 10340Sodium CarbonateHCID 11776TriphenylphosphineHCID 27339863-Fluorophenylboronic acidHCID 866357834-Amino-7-bromo-5-{4-[({[4-(trifluoromethyl)pyridin-2-yl]amino}carbonyl)amino]phenyl}pyrrolo[2,1-f][1,2,4-]triazine-6-carboxylate

Produkt 1

HCID 57955236Ethyl 4-amino-7-(3-fluorophenyl)-5-{4-[({[4-(trifluoromethyl)pyridin-2-yl]amino}carbonyl)amino]phenyl}-pyrrolo[2,1-f][1,2,4]triazine-6-carboxylateAusbeute 383,5 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 167845palladium(II) acetateKatalysatorHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

Palladium(II)acetate (0.002 g, 0.009 mmol) was dissolved in dioxane (0.5 mL), and treated with triphenylphosphine (0.009 g, 0.035 mmol). The mixture was degassed twice before adding ethyl Intermediate AY (4-amino-7-bromo-5-{4-[({[4-(trifluoromethyl)pyridin-2-yl]amino}carbonyl)amino]phenyl}pyrrolo[2,1-f][1,2,4-]triazine-6-carboxylate (0.05 g, 0.009 mmol)), 3-fluorophenylboronic acid (0.014 g, 0.097 mmol) and aq. Na2CO3 solution (0.11 mL, 0.22 mmol, 2M). The mixture was heated to 80° C. overnight. The reaction was then cooled and filtered through silica. The filtrate was concentrated then triturated with EtOAc. The product was collected by filtration to give 20 mg of a tan solid (39%). 1H-NMR (THF-d8) δ 10.59 (bs, 1H) 9.08 (s, 1H), 8.47 (d, J=5.1, 1H), 7.79 (s, 1H), 7.73-7.68 (m, 3H), 7.41-7.37 (m, 5H), 7.23 (d, J=5.2, 1H), 7.13-7.08 (m, 1H), 3.94 (q, J=7.1, 2H), 0.90 (t, J=7.1, 3H); MS [M+H]+=580.0; LCMS RT=3.41.

Aufarbeitung

  1. customThe mixture was degassed twice
  2. temperatureThe reaction was then cooled
  3. filtrationfiltered through silica
  4. concentrationThe filtrate was concentrated
  5. customthen triturated with EtOAc
  6. filtrationThe product was collected by filtration

Quellen und Nachweise

ORD-Eintrag
ord-d0121405b2dc484cb5fd70fbfe4e58aa
Quelldatensatz
uspto-grants-2012_03
Patentnummer
US08133995B2

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