1-Hydroxybenzotriazole → 2-(6-chloro-4-fluoro-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-2-methoxy-1-methyl-ethyl)-amide

HRID 246164Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 246164
[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11]3[N:12]=[C:13]4[C:19]([C:20]([OH:22])=O)=[CH:18][N:17]([CH2:23][O:24][CH2:25][CH2:26][Si:27]([CH3:30])([CH3:29])[CH3:28])[C:14]4=[N:15][CH:16]=3)=[N:7][NH:8]2)=[C:4]([F:31])[CH:3]=1.Cl.[CH3:33][O:34][CH2:35][C@@H:36]([NH2:38])[CH3:37].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C1C=CC2N(O)N=NC=2C=1.C(N(CC)C(C)C)(C)C>CN(C=O)C>[CH3:33][O:34][CH2:35][C@@H:36]([NH:38][C:20]([C:19]1[C:13]2[C:14](=[N:15][CH:16]=[C:11]([C:6]3[C:5]4[C:9](=[CH:10][C:2]([Cl:1])=[CH:3][C:4]=4[F:31])[NH:8][N:7]=3)[N:12]=2)[N:17]([CH2:23][O:24][CH2:25][CH2:26][Si:27]([CH3:28])([CH3:30])[CH3:29])[CH:18]=1)=[O:22])[CH3:37]

Komponenten

7

Edukt 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 54596079(2S)-1-methoxypropan-2-amine hydrochlorideHCID 712801642-(6-chloro-4-fluoro-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid

Produkt 1

HCID 712860522-(6-chloro-4-fluoro-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-2-methoxy-1-methyl-ethyl)-amideAusbeute 89,6 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

A 25 mL round-bottomed flask was charged with 2-(6-chloro-4-fluoro-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (0.39 g, 0.84 mmol), (S)-1-methoxypropan-2-amine hydrochloride (253 mg, 2.0 mmol), HBTU (457 mg, 1.27 mmol), and HOBT (125 mg, 0.93 mmol). Then added DMF (2 mL) followed by N,N-diisopropylethylamine (0.59 mL, 3.38 mmol). The yellow reaction mixture was stirred at room temperature overnight then quenched with water and extracted with EtOAc (30 mL). The organic layer was washed once with saturated NaHCO3 and water. The combined aqueous layers were back extracted with EtOAc (25 mL). The combined organic layers was dried over sodium sulfate, filtered and concentrated. The residue was purified by chromatography over SiO2 with EtOAc/heptane (gradient: 0-100% EtOAc) to afford 401 mg (89%) of 2-(6-chloro-4-fluoro-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-2-methoxy-1-methyl-ethyl)-amide as a light yellow solid. MS: [M+H]+=533.

Aufarbeitung

  1. customthen quenched with water
  2. extractionextracted with EtOAc (30 mL)
  3. washThe organic layer was washed once with saturated NaHCO3 and water
  4. extractionThe combined aqueous layers were back extracted with EtOAc (25 mL)
  5. dry with materialThe combined organic layers was dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by chromatography over SiO2 with EtOAc/heptane (gradient: 0-100% EtOAc)

Quellen und Nachweise

ORD-Eintrag
ord-f245fa97dc2f40618fc9beb3c02af8fe
Quelldatensatz
uspto-grants-2014_02
Patentnummer
US08658646B2

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