2-Butanamine, 2-methyl- → 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-N-tert-pentyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

HRID 246572

Reaktionsgleichung

Reaktionsgleichung von HRID 246572
[F:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:12]3[N:13]=[C:14]4[C:20]([C:21](O)=[O:22])=[CH:19][NH:18][C:15]4=[N:16][CH:17]=3)=[N:7][N:8]2[CH3:11])=[CH:4][CH:3]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[CH3:57][C:58]([NH2:62])([CH2:60][CH3:61])[CH3:59]>CN(C=O)C>[F:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:12]3[N:13]=[C:14]4[C:20]([C:21]([NH:62][C:58]([CH2:60][CH3:61])([CH3:59])[CH3:57])=[O:22])=[CH:19][NH:18][C:15]4=[N:16][CH:17]=3)=[N:7][N:8]2[CH3:11])=[CH:4][CH:3]=1

Komponenten

6

Edukt 4

HCID 689862-Butanamine, 2-methyl-HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 712796392-(6-fluoro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid

Produkt 1

HCID 712803232-(6-fluoro-1-methyl-1H-indazol-3-yl)-N-tert-pentyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxamideAusbeute 20,8 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

To a stirred solution of 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (59 mg, 0.19 mmol), HATU (91.20 mmol, 0.24 mmol) and DIPEA (49 mg, 0.38 mmol) in 6 mL of DMF, 2-methylbutan-2-amine (21.60 mg, 0.24 mmol) was added in one portion at room temperature. Then the reaction mixture was stirred for 16 hours. The solvent was evaporated at 70° C. under reduced pressure and the residue was purified by preparative-HPLC (Gemini 5u C18 150×21.2 mm; inject volume: 3 mL/inj, flow rate: 20 mL/min; wavelength: 214 nm and 254 nm; the gradient conditions were: 15% acetonitrile/75% water (0.1% trifluoroacetic acid, v/v) initially, proceeding to 70% acetonitrile/30% water (0.1% trifluoroacetic acid, v/v) in a linear fashion after 9 min.) to give 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-N-tert-pentyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (15 mg, 20.7%) as a white solid. MS: (M+H)+=381; 1H NMR (300 MHz, DMSO): δ 12.82 (s, 1H), 9.07 (s, 1H), 8.47-8.37 (m, 2H), 7.81 (s, 1H), 7.70 (dd, 1H, J=9.6, 2.1 Hz), 7.17 (t, 1H, J=2.1 Hz), 4.15 (s, 3H), 1.89 (q, 2H, J=7.6 Hz), 1.46 (s, 6H), 0.87 (t, 3H, J=7.5 Hz).

Aufarbeitung

  1. customThe solvent was evaporated at 70° C. under reduced pressure
  2. customthe residue was purified by preparative-HPLC (Gemini 5u C18 150×21.2 mm
  3. wait15% acetonitrile/75% water (0.1% trifluoroacetic acid, v/v) initially, proceeding to 70% acetonitrile/30% water (0.1% trifluoroacetic acid, v/v) in a linear fashion after 9 min.

Quellen und Nachweise

ORD-Eintrag
ord-79db010e2b5345048bc3391370fce2d9
Quelldatensatz
uspto-grants-2014_02
Patentnummer
US08658646B2

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