2-Amino-2-methyl-1-propanol → N-(1-hydroxy-2-methylpropan-2-yl)-2-(5-methoxy-1-methyl-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

HRID 246393

Reaktionsgleichung

Reaktionsgleichung von HRID 246393
CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH2:25][C:26]([CH3:30])([CH3:29])[CH2:27][OH:28].[CH3:31][O:32][C:33]1[CH:34]=[C:35]2[C:39](=[CH:40][CH:41]=1)[N:38]([CH3:42])[N:37]=[C:36]2[C:43]1[N:44]=[C:45]2[C:51]([C:52](O)=[O:53])=[CH:50][N:49]([CH2:55][O:56][CH2:57][CH2:58][Si:59]([CH3:62])([CH3:61])[CH3:60])[C:46]2=[N:47][CH:48]=1>CN(C=O)C>[OH:28][CH2:27][C:26]([NH:25][C:52]([C:51]1[C:45]2[C:46](=[N:47][CH:48]=[C:43]([C:36]3[C:35]4[C:39](=[CH:40][CH:41]=[C:33]([O:32][CH3:31])[CH:34]=4)[N:38]([CH3:42])[N:37]=3)[N:44]=2)[N:49]([CH2:55][O:56][CH2:57][CH2:58][Si:59]([CH3:60])([CH3:62])[CH3:61])[CH:50]=1)=[O:53])([CH3:30])[CH3:29]

Komponenten

5

Edukt 3

HCID 118072-Amino-2-methyl-1-propanolHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 712798522-(5-methoxy-1-methyl-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid

Produkt 1

HCID 71280154N-(1-hydroxy-2-methylpropan-2-yl)-2-(5-methoxy-1-methyl-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamideAusbeute 100 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
25 °C

Versuchsvorschrift

In a 16×100 mm screw cap test tube were added HATU (40.2 mg, 106 μmol.20) and 2-amino-2-methylpropan-1-ol (31.4 mg, 353 μmol) then 2-(5-methoxy-1-methyl-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (40 mg, 88.2 mmol) dissolved in DMF (2.00 mL) was added to give a light yellow solution. The reaction mixture stirred at 25° C. overnight, solvents evaporated and residue purified by chromatography (spherical silica 20-45 μm, 23 g, Versaflash Supelco) eluting with 0 to 50% EtOAc in hexanes over 25 min to yield N-(1-hydroxy-2-methylpropan-2-yl)-2-(5-methoxy-1-methyl-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (46.3 mg, 88.2 μmol, 100%) as an off-white solid. MS (M+Na)+=547 (>90% purity); 1H NMR (CDCl3) δ: 9.14 (s, 1H), 8.49 (s, 1H), 8.32 (s, 1H), 7.85 (d, J=2.3 Hz, 1H), 7.41 (d, J=9.1 Hz, 1H), 7.20 (dd, J=9.3, 2.5 Hz, 1H), 5.72 (s, 2H), 4.18 (s, 3H), 3.92 (s, 3H), 3.78 (s, 2H), 3.54-3.65 (m, 2H), 1.53 (s, 6H), 0.91-1.01 (m, 2H), −0.03 (s, 9H).

Aufarbeitung

  1. customIn a 16×100 mm screw cap test tube
  2. additionwas added
  3. customto give a light yellow solution
  4. customsolvents evaporated
  5. customresidue purified by chromatography (spherical silica 20-45 μm, 23 g, Versaflash Supelco)
  6. washeluting with 0 to 50% EtOAc in hexanes over 25 min

Quellen und Nachweise

ORD-Eintrag
ord-6219929a03254669984f45251abe1386
Quelldatensatz
uspto-grants-2014_02
Patentnummer
US08658646B2

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