Reaktion #2371770

Reaktionsgleichung

5-(2-(4-fluoro-3-methylphenyl)pyridin-3-yl)-1H-indazole-7-carboxylic acid

HBTU

morpholine

NEt3

→

(5-(2-(4-fluoro-3-methylphenyl)pyridin-3-yl)-1H-indazol-7-yl)(morpholino)methanone

Lösungsmittel

acetonitrile

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.ADDITIONA capped vial containing a stir-bar
2. 2
   Einengenthe reaction mixture was concentrated
3. 3
   workup.ADDITIONdiluted with EtOAc (15 mL)/H2O (5 mL)
4. 4
   SonstigeOrganic layer was separated
5. 5
   Waschenwashed with brine
6. 6
   Trocknendried over anhydrous Na2SO4
7. 7
   Einengenconcentrated
8. 8
   Sonstigepurified by preparative HPLC
9. 9
   EinengenProduct fractions were concentrated
10. 10
    workup.ADDITIONdiluted with water and neutralized with aq. Na2CO3 solution
11. 11
    FiltrationThe resulting white precipitate was filtered
12. 12
    Sonstigedried

Vorschrift

A capped vial containing a stir-bar, was charged with 5-(2-(4-fluoro-3-methylphenyl)pyridin-3-yl)-1H-indazole-7-carboxylic acid (100 mg, 0.28 mmol), HBTU (140 mg, 0.36 mmol), morpholine (29 mg, 0.03 mL, 0.34 mmol), NEt3 (57 mg, 0.08 mL, 0.57 mmol) and acetonitrile (3 ml) successively and stirred the contents at room temperature. After 12 h, the reaction mixture was concentrated and diluted with EtOAc (15 mL)/H2O (5 mL). Organic layer was separated, washed with brine, dried over anhydrous Na2SO4, concentrated and purified by preparative HPLC. Product fractions were concentrated, diluted with water and neutralized with aq. Na2CO3 solution. The resulting white precipitate was filtered and dried to obtain (5-(2-(4-fluoro-3-methylphenyl)pyridin-3-yl)-1H-indazol-7-yl)(morpholino)methanone. 1H NMR (DMSO-d6): δ 13.27 (s, 1H), 8.66 (d, 1H, J=4.7 Hz), 8.17 (s, 1H), 7.97-7.92 (m, 2H), 7.48 (dd, 1H, J=4.9 and 7.6 Hz), 7.33 (d, 1H, J=7.8 Hz), 6.97-6.88 (m, 3H), 3.62-3.42 (m, 8H), 2.10 (s, 3H).19F NMR (DMSO-d6): δ −118.69 (s).LCMS: rt 4.45 min (A), purity 97%, MS (m/e) 417 (MH+)

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