Diisopropylethylamine → 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-1-(4-trifluoromethyl-pyridin-2-yl)-ethyl]-amide

HRID 246016Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 246016
Cl.Cl.[F:3][C:4]([F:15])([F:14])[C:5]1[CH:10]=[CH:9][N:8]=[C:7]([C@H:11]([NH2:13])[CH3:12])[CH:6]=1.C(N(CC)C(C)C)(C)C.[F:25][C:26]1[CH:34]=[C:33]2[C:29]([C:30]([C:36]3[N:37]=[C:38]4[C:44]([C:45](O)=[O:46])=[CH:43][N:42]([CH2:48][O:49][CH2:50][CH2:51][Si:52]([CH3:55])([CH3:54])[CH3:53])[C:39]4=[N:40][CH:41]=3)=[N:31][N:32]2[CH3:35])=[CH:28][CH:27]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[F:15][C:4]([F:14])([F:3])[C:5]1[CH:10]=[CH:9][N:8]=[C:7]([C@H:11]([NH:13][C:45]([C:44]2[C:38]3[C:39](=[N:40][CH:41]=[C:36]([C:30]4[C:29]5[C:33](=[CH:34][C:26]([F:25])=[CH:27][CH:28]=5)[N:32]([CH3:35])[N:31]=4)[N:37]=3)[N:42]([CH2:48][O:49][CH2:50][CH2:51][Si:52]([CH3:55])([CH3:54])[CH3:53])[CH:43]=2)=[O:46])[CH3:12])[CH:6]=1

Komponenten

6

Edukt 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 712796202-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acidHCID 86677935(R)-1-(4-trifluoromethylpyridin-2-yl)-ethylamine dihydrochloride

Produkt 1

HCID 712882332-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-1-(4-trifluoromethyl-pyridin-2-yl)-ethyl]-amideAusbeute 88 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

To a solution of (R)-1-(4-trifluoromethyl-pyridin-2-yl)-ethylamine dihydrochloride (89 mg, 0.34 mmol) in DMF (2 mL) was added N,N-diisopropylethylamine (0.20 mL, 1.13 mmol), 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (100 mg, 0.23 mmol), and HATU (95 mg, 0.25 mmol). The yellow reaction mixture was stirred at room temperature overnight then quenched with water and extracted with EtOAc (3×). The combined organics were washed with water (3×) and brine then dried over MgSO4 and concentrated. The residue was purified by silica gel chromatography with 50% to 100% EtOAc/hexanes to give 122 mg (88%) 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-(4-trifluoromethyl-pyridin-2-yl)-ethyl]-amide as a white solid.

Aufarbeitung

  1. customthen quenched with water
  2. extractionextracted with EtOAc (3×)
  3. washThe combined organics were washed with water (3×) and brine
  4. dry with materialthen dried over MgSO4
  5. concentrationconcentrated
  6. customThe residue was purified by silica gel chromatography with 50% to 100% EtOAc/hexanes

Quellen und Nachweise

ORD-Eintrag
ord-a24a589e3721447e804587b1484f8a3f
Quelldatensatz
uspto-grants-2014_02
Patentnummer
US08658646B2

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