1-(7-Amino-3,4-dihydroisoquinolin-2(1H)-YL)-2,2,2-trifluoroethanone → Trifluoroacetamide pyrazolopyridazine

HRID 1159897Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1159897
ClC1N=C(C2C(C3C=C(NC(=O)C4C(F)=CC=CC=4F)C=CC=3)=[N:10][N:11]3C=CC=CC=23)C=CN=1.[F:34][C:35]([F:50])([F:49])[C:36]([N:38]1CCC2[C:40](=[CH:41][C:42]([NH2:48])=[CH:43]C=2)[CH2:39]1)=[O:37]>CC(O)C>[NH:10]1[C:41]2[CH:40]=[CH:39][N:38]=[N:48][C:42]=2[CH:43]=[N:11]1.[F:34][C:35]([F:50])([F:49])[C:36]([NH2:38])=[O:37]

Komponenten

4

Edukt 2

HCID 107527801-(7-Amino-3,4-dihydroisoquinolin-2(1H)-YL)-2,2,2-trifluoroethanoneHCID 59513803N-{3-[3-(2-Chloro-4-pyrimidinyl)pyrazolo[1,5-a]pyridin-2-yl]phenyl}-2,6-difluorobenzamide

Produkt 1

HCID 86618777Trifluoroacetamide pyrazolopyridazineAusbeute 349,1 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 3776IsopropanolLösungsmittel

Reaktionsbedingungen

Temperatur
160 °C

Versuchsvorschrift

A mixture of N-{3-[3-(2-chloro-4-pyrimidinyl)pyrazolo[1,5-a]pyridin-2-yl]phenyl}-2,6-difluorobenzamide (200 mg, 0.43 mmol) and 2-(trifluoroacetyl)-1,2,3,4-tetrahydro-7-isoquinolinamine (211 mg, 0.86 mmol) in a few mL i-PrOH was heated in a microwave apparatus at 160° C. until the reaction was complete. The by partitioning the reaction mixture between saturated aqueous NaHCO3 and CHCl3. The organic layer was washed with brine, dried over Na2SO4, filtered and concentrated to give a residue that was purified by silica gel chromatography to afford the intermediate trifluoroacetamide pyrazolopyridazine (350 mg). A portion of this material (250 mg) was subjected to similar conditions as described in Example 62, step F to afford the title compound (198 mg) as a tan powder. LC-MS (AP)+=574.07. 1H NMR (400 MHz, DMSO-d6) δ 2.59 (t, 2H, J=5.5), 2.89 (t, 2H, J=5.5), 3.74 (s, 2H), 6.46 (d, 1H, J=5.1), 6.90 (d, 1H, J=8.2), 7.10 (t, 1H, J=6.7), 7.22 (d, 1H, J=8.0), 7.24 (d, 1H, J=7.9), 7.32 (s, 1H, 7.34 (s, 1H), 7.44-7.48 (m, 3H), 7.53-7.60 (m, 1H), 7.80 (d, 1H, J=8.0), 7.97 (s, 1H), 8.21 (d, 1H, J=5.3), 8.46 (d, 1H, J=9.1), 8.82 (d, 1H, J=6.7), 9.37 (s, 1H).

Aufarbeitung

  1. customThe by partitioning the reaction mixture between saturated aqueous NaHCO3 and CHCl3
  2. washThe organic layer was washed with brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto give a residue that
  7. customwas purified by silica gel chromatography

Quellen und Nachweise

ORD-Eintrag
ord-623f42e7bad04e7b8c8a46cd85a44a54
Quelldatensatz
uspto-grants-2010_10
Patentnummer
US07812022B2

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