Reaktion #160888

Reaktionsgleichung

5-bromo-6-methyl-7-(1,4-oxazepan-4-ylmethyl)pyrrolo[2,1-f][1,2,4]triazin-4-amine

1-[2-fluoro-5-(trifluoromethyl)phenyl]-3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]urea

K2CO3

H2O

→

desired product

Ausbeute 15.0%

N-{4-[4-amino-6-methyl-7-(1,4-oxazepan-4-ylmethyl)pyrrolo[2,1-f][1,2,4]triazin-5-yl]phenyl}-N′-[2-fluoro-5-(trifluoromethyl)phenyl]urea

Ausbeute 15.0%

Lösungsmittel

1,4 dioxane

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeThe mixture was degassed
2. 2
   Temperaturcooled to rt
3. 3
   SonstigeThe mixture was partitioned between ethyl acetate (25 mL) and saturated aqueous Na2CO3 solution (25 mL)
4. 4
   SonstigeThe layers were separated
5. 5
   Waschenthe organic phase was washed
6. 6
   Trocknendried (Na2SO4)
7. 7
   Einengenconcentrated to dryness
8. 8
   SonstigeThe residue was purified by preparative HPLC
9. 9
   Waschena gradient elution from 10% to 70% acetonitrile

Vorschrift

To a stirred solution of 5-bromo-6-methyl-7-(1,4-oxazepan-4-ylmethyl)pyrrolo[2,1-f][1,2,4]triazin-4-amine (100 mg, 0.29 mmol) and tetrakis(triphenylphosphine)-palladium(0) (101 mg, 0.088 mmol), in degassed 1,4 dioxane (4.0 mL), was added Intermediate AAN (1-[2-fluoro-5-(trifluoromethyl)phenyl]-3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]urea) (248 mg, 0.59 mmol), K2CO3 (162 mg, 1.18 mmol), and H2O (0.4 mL). The mixture was degassed and heated (90° C.) for 17 h and then cooled to rt. The mixture was partitioned between ethyl acetate (25 mL) and saturated aqueous Na2CO3 solution (25 mL). The layers were separated and the organic phase was washed, dried (Na2SO4), and concentrated to dryness. The residue was purified by preparative HPLC using a gradient elution from 10% to 70% acetonitrile to obtain 24 mg (15%) of the desired product. 1H-NMR (DMSO-d6) δ 9.36 (s, 1H), 8.98-8.97 (m, 1H), 8.63 (dd, J=2.4, 7.2 Hz, 1H), 7.85 (s, 1H), 7.60-7.47 (m, 3H), 7.41-7.33 (m, 1H), 7.33 (d, J=8.7 Hz, 2H), 3.95 (s, 2H), 3.66 (t, J=6.0 Hz, 2H), 3.59-3.56 (m, 2H), 3.31 (m, 2H), 2.68-2.62 (m, 4H), 2.10 (s, 3H), 1.83-1.75 (m, 2H); MS [M+H]+=558.1; LCMS RT=2.94.

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