Potassium Carbonate → Tert-butyl 4-[4-[6-amino-5-(1,3-benzoxazol-2-yl)-3-pyridyl]-3-formyl-pyrazol-1-yl]piperidine-1-carboxylate

HRID 908467Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 908467
[O:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[C:10]1[C:11]([NH2:25])=[N:12][CH:13]=[C:14](B2OC(C)(C)C(C)(C)O2)[CH:15]=1.Br[C:27]1[C:28]([CH:45]=[O:46])=[N:29][N:30]([CH:32]2[CH2:37][CH2:36][N:35]([C:38]([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:39])[CH2:34][CH2:33]2)[CH:31]=1.C(=O)([O-])[O-].[K+].[K+]>C(#N)C.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[NH2:25][C:11]1[N:12]=[CH:13][C:14]([C:27]2[C:28]([CH:45]=[O:46])=[N:29][N:30]([CH:32]3[CH2:33][CH2:34][N:35]([C:38]([O:40][C:41]([CH3:42])([CH3:44])[CH3:43])=[O:39])[CH2:36][CH2:37]3)[CH:31]=2)=[CH:15][C:10]=1[C:2]1[O:1][C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=1

Komponenten

6

Edukt 3

HCID 11430Potassium CarbonateHCID 673889123-(1,3-Benzoxazol-2-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-amineHCID 86630149Tert-butyl 4-(4-bromo-3-formyl-pyrazol-1-yl)piperidine-1-carboxylate

Produkt 1

HCID 86630148Tert-butyl 4-[4-[6-amino-5-(1,3-benzoxazol-2-yl)-3-pyridyl]-3-formyl-pyrazol-1-yl]piperidine-1-carboxylateAusbeute 85,1 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumKatalysatorHCID 6342AcetonitrileLösungsmittel

Versuchsvorschrift

A suspension of 3-(1,3-benzoxazol-2-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-amine (0.3 g), tert-butyl 4-(4-bromo-3-formyl-pyrazol-1-yl)piperidine-1-carboxylate (0.362 g), potassium carbonate (0.335 g) and tetrakis(triphenylphosphine) palladium (0.093 g) in degassed acetonitrile (50 mL) was stirred at reflux overnight. The resulting suspension was cooled to room temperature, filtered, washed with dichloromethane (3×20 ml) and the filtrate concentrated and the crude product was purified by flash chromatography on silica gel eluting with 5 to 90% ethyl acetate in petroleum ether. The solvent was evaporated to dryness to afford tert-butyl 4-[4-[6-amino-5-(1,3-benzoxazol-2-yl)-3-pyridyl]-3-formyl-pyrazol-1-yl]piperidine-1-carboxylate (0.370 g) as a solid. NMR Spectrum: (DMSOd6) 1.44 (s, 9H), 1.87 (dd, 1H), 1.92 (dd, 1H), 2.09-2.18 (m, 2H), 2.97 (bs, 2H), 4.04-4.16 (m, 2H), 4.52-4.61 (m, 1H), 7.41-7.49 (m, 2H), 7.80 (dd, 1H), 7.82 (bs, 2H), 7.85 (dd, 1H), 8.48 (s, 1H), 8.56 (d, 1H), 8.65 (d, 1H), 9.99 (s, 1H); Mass spectrum: M+H+ 489.

Aufarbeitung

  1. temperatureat reflux overnight
  2. filtrationfiltered
  3. washwashed with dichloromethane (3×20 ml)
  4. concentrationthe filtrate concentrated
  5. customthe crude product was purified by flash chromatography on silica gel eluting with 5 to 90% ethyl acetate in petroleum ether
  6. customThe solvent was evaporated to dryness

Quellen und Nachweise

ORD-Eintrag
ord-589819ecef004ca6be7b613bf6f41505
Quelldatensatz
uspto-grants-2011_09
Patentnummer
US08017611B2

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