Aniline → 2-(6-chloro-1-methyl-1H-indazol-3-yl)-N-phenyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

HRID 246600

Reaktionsgleichung

Reaktionsgleichung von HRID 246600
[Cl: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]([OH:23])=O)=[CH:19][NH:18][C:15]4=[N:16][CH:17]=3)=[N:7][N:8]2[CH3:11])=[CH:4][CH:3]=1.[NH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.CCN=C=NCCCN(C)C.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C1C=CN=CC=1)C.CN(C=O)C>[Cl: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:24][C:25]5[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=5)=[O:23])=[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

8

Edukt 5

HCID 6115AnilineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 712800962-(6-chloro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid

Produkt 1

HCID 712796492-(6-chloro-1-methyl-1H-indazol-3-yl)-N-phenyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxamideAusbeute 29 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 142844-(Dimethylamino)pyridineKatalysatorHCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

A mixture of 2-(6-chloro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (0.07 g, 0.3 mmol), aniline (0.05 g, 0.54 mmol), EDCI (0.057 g, 0.3 mmol), DMAP (0.037 g, 0.3 mmol), and DIPEA (0.163 g, 1.26 mmol) in 10 mL of DMF was stirred at room temperature for 5 hours. And then HATU (0.114 g, 0.3 mmol) was added, the final reaction mixture was stirred for 15 hours. The solvent was removed under reduced pressure at 70° C. The residue was triturated with water and then 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: 65% acetonitrile/35% water (0.1% trifluoroacetic acid, v/v) initially, proceeding to 72% acetonitrile/28% water (0.1% trifluoroacetic acid, v/v) in a linear fashion over 9 min.) to give 2-(6-chloro-1-methyl-1H-indazol-3-yl)-N-phenyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (0.025 g, 29%) as a white solid. MS: (M+H)+=403; 1H NMR (300 MHz, DMSO): δ 10.21 (s, 1H), 9.12 (s, 1H), 8.63-8.58 (m, 2H), 8.42 (brs, 2H), 8.04 (s, 1H), 7.83-7.80 (m, 2H), 7.49-7.43 (m, 2H), 7.30 (d, 1H, J=8.7 Hz), 7.17 (d, 1H, J=7.2 Hz), 4.21 (s, 3H).

Aufarbeitung

  1. customthe final reaction mixture
  2. stirringwas stirred for 15 hours
  3. customThe solvent was removed under reduced pressure at 70° C
  4. customThe residue was triturated with water
  5. custompurified by preparative-HPLC (Gemini 5u C18 150×21.2 mm
  6. wait65% acetonitrile/35% water (0.1% trifluoroacetic acid, v/v) initially, proceeding to 72% acetonitrile/28% water (0.1% trifluoroacetic acid, v/v) in a linear fashion over 9 min.

Quellen und Nachweise

ORD-Eintrag
ord-58ec797298ba492a96a5a76568928180
Quelldatensatz
uspto-grants-2014_02
Patentnummer
US08658646B2

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