Methylamine → 5-(2-Fluoro-4-iodophenylamino)-N-methylimidazo[1,5-a]pyrazine-6-carboxamide

HRID 2064039Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2064039
CO[C:3]([C:5]1[N:6]=[CH:7][C:8]2[N:9]([CH:20]=[N:21][CH:22]=2)[C:10]=1[NH:11][C:12]1[CH:17]=[CH:16][C:15]([I:18])=[CH:14][C:13]=1[F:19])=[O:4].[CH3:23][NH2:24].C1COCC1>CO.C(OCC)(=O)C>[F:19][C:13]1[CH:14]=[C:15]([I:18])[CH:16]=[CH:17][C:12]=1[NH:11][C:10]1[N:9]2[CH:20]=[N:21][CH:22]=[C:8]2[CH:7]=[N:6][C:5]=1[C:3]([NH:24][CH3:23])=[O:4]

Komponenten

6

Edukt 3

HCID 6329MethylamineHCID 8028TetrahydrofuranHCID 591401715-(2-Fluoro-4-iodo-phenylamino)-imidazo[1,5-a]pyrazine-6-carboxylic acid methyl ester

Produkt 1

HCID 441359845-(2-Fluoro-4-iodophenylamino)-N-methylimidazo[1,5-a]pyrazine-6-carboxamideAusbeute 44,8 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 887MethanolLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

To a solution of 5-(2-fluoro-4-iodo-phenylamino)-imidazo[1,5-a]pyrazine-6-carboxylic acid methyl ester (108 mg, 0.26 mmol) in anhydrous methanol (0.5 mL) was added 2M methylamine in THF (1.3 mL, 2.6 mmol, 10 eq), and the reaction mixture was stirred at room temperature under N2 for 3 days. The reaction mixture was diluted with ethyl acetate (50 mL). The organic layer was washed with water and brine, dried (Na2SO4), filtered and concentrated in vacuo. The resultant residue was subjected to reverse-phase preparative HPLC [Gemini-NX (100× 30 mm, 10 micron), 0.1% FA in water/acetonitrile, 5-85%, ramp time in 10 minutes, flow at 60 ml/min] to afford the title compound as a white solid (48.3 mg, 44.8%). 1H NMR (DMSO-d6, 400 MHz) δ ppm 10.89 (s, 1H), 8.95 to 8.91 (m, 1H), 8.86 (s, 1H), 7.92 (s, 1H), 7.88 (s, 1H), 7.76 (dd, J=8.4 Hz, 1.2 Hz, 1H), 7.44 (d, J=6.8 Hz, 1H), 6.51 (t, J=6.8 Hz, 1H), 2.81 (d, 4.0 Hz, 3H); LCMS (method E2): RT=12.23 min, [M+H]+=412.

Aufarbeitung

  1. washThe organic layer was washed with water and brine
  2. dry with materialdried (Na2SO4)
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customwas subjected to reverse-phase preparative HPLC [Gemini-NX (100× 30 mm, 10 micron), 0.1% FA in water/acetonitrile, 5-85%, ramp time in 10 minutes, flow at 60 ml/min]

Quellen und Nachweise

ORD-Eintrag
ord-90e2c2beca534d2586055cabddc0ac5d
Quelldatensatz
uspto-grants-2012_10
Patentnummer
US08288408B2

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