Triethylamine → 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((R)-1-cyanomethyl-pyrrolidin-3-yl)-amide

HRID 246232Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 246232
[NH:1]1[CH2:5][CH2:4][C@@H:3]([NH:6][C:7]([C:9]2[C:17]3[C:12](=[N:13][CH:14]=[C:15]([C:18]4[C:26]5[C:21](=[CH:22][C:23]([F:27])=[CH:24][CH:25]=5)[N:20]([CH3:28])[N:19]=4)[N:16]=3)[N:11]([CH2:29][O:30][CH2:31][CH2:32][Si:33]([CH3:36])([CH3:35])[CH3:34])[CH:10]=2)=[O:8])[CH2:2]1.[CH2:37]([N:39](CC)CC)[CH3:38]>ClCCl.BrCC#N>[C:37]([CH2:38][N:1]1[CH2:5][CH2:4][C@@H:3]([NH:6][C:7]([C:9]2[C:17]3[C:12](=[N:13][CH:14]=[C:15]([C:18]4[C:26]5[C:21](=[CH:22][C:23]([F:27])=[CH:24][CH:25]=5)[N:20]([CH3:28])[N:19]=4)[N:16]=3)[N:11]([CH2:29][O:30][CH2:31][CH2:32][Si:33]([CH3:36])([CH3:35])[CH3:34])[CH:10]=2)=[O:8])[CH2:2]1)#[N:39]

Komponenten

5

Edukt 2

HCID 8471TriethylamineHCID 712883352-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (R)-pyrrolidin-3-ylamide

Produkt 1

HCID 866779632-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((R)-1-cyanomethyl-pyrrolidin-3-yl)-amideAusbeute 45 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6344DichloromethaneLösungsmittelHCID 11534BromoacetonitrileLösungsmittel

Versuchsvorschrift

2-(6-Fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (R)-pyrrolidin-3-ylamide from Step 1 was dissolved in dichloromethane with the addition of triethylamine and bromo-acetonitrile. The reaction was concentrated and dried from mixtures of dichloromethane and hexanes. The crude was dissolved in a mixture dichloromethane, tetrahydrofuran, and methanol, supported on silica gel and purified by flash chromatography (4 g silicycle) with 0% to 10% MeOH in dichloromethane (0.5% Et3N). The appropriate fractions were combined and concentrated. The solid obtained was triturated with Et2O and hexanes. The solid was discarded and the mother liquor was concentrated to afford 220 mg (45%) of 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((R)-1-cyanomethyl-pyrrolidin-3-yl)-amide as a white solid, 220 mg (45% yield). LC-MS (M+H)+=549.

Aufarbeitung

  1. concentrationThe reaction was concentrated
  2. dry with materialdried from mixtures of dichloromethane and hexanes
  3. dissolutionThe crude was dissolved in a mixture dichloromethane, tetrahydrofuran, and methanol
  4. custompurified by flash chromatography (4 g silicycle) with 0% to 10% MeOH in dichloromethane (0.5% Et3N)
  5. concentrationconcentrated
  6. customThe solid obtained
  7. customwas triturated with Et2O and hexanes
  8. concentrationthe mother liquor was concentrated

Quellen und Nachweise

ORD-Eintrag
ord-63e0407c83e942298d0fa81b70ceefa0
Quelldatensatz
uspto-grants-2014_02
Patentnummer
US08658646B2

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