Potassium Carbonate → tert-Butyl ((1S)-1-(6-(3,5-dimethylisoxazol-4-yl)-1-methyl-1H-pyrrolo[3,2-b]pyridin-5-yl)ethyl)carbamate

HRID 75306Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 75306
Br[C:2]1[CH:3]=[C:4]2[N:20]([CH3:21])[CH:19]=[CH:18][C:5]2=[N:6][C:7]=1[C@@H:8]([NH:10][C:11](=[O:17])[O:12][C:13]([CH3:16])([CH3:15])[CH3:14])[CH3:9].[CH3:22][C:23]1[C:27](B2OC(C)(C)C(C)(C)O2)=[C:26]([CH3:37])[O:25][N:24]=1.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.CCOC(C)=O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl>[CH3:22][C:23]1[C:27]([C:2]2[CH:3]=[C:4]3[N:20]([CH3:21])[CH:19]=[CH:18][C:5]3=[N:6][C:7]=2[C@@H:8]([NH:10][C:11](=[O:17])[O:12][C:13]([CH3:16])([CH3:15])[CH3:14])[CH3:9])=[C:26]([CH3:37])[O:25][N:24]=1

Komponenten

7

Edukt 3

HCID 11430Potassium CarbonateHCID 27586563,5-Dimethylisoxazole-4-boronic acid pinacol esterHCID 86707985(S)-tert-butyl (1-(6-bromo-1-methyl-1H-pyrrolo[3,2-b]pyridin-5-yl)ethyl)carbamate

Produkt 1

HCID 86708005tert-Butyl ((1S)-1-(6-(3,5-dimethylisoxazol-4-yl)-1-methyl-1H-pyrrolo[3,2-b]pyridin-5-yl)ethyl)carbamate

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178418807HCID 178418807, VerbindungKatalysatorHCID 8857Ethyl AcetateLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Versuchsvorschrift

A solution of (S)-tert-butyl (1-(6-bromo-1-methyl-1H-pyrrolo[3,2-b]pyridin-5-yl)ethyl)carbamate (100 mg, 0.282 mmol), 3,5-dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isoxazole (126 mg, 0.565 mmol) and PdCl2(dppf)-CH2Cl2 adduct (11 mg, 0.014 mmol) in dioxane (1.0 mL) and 3 M aqueous potassium carbonate (1.01 mL, 3.02 mmol) were heated at 120° C. for 1 hour in a microwave reactor. The mixture was diluted with EtOAc (50 mL), washed with saturated aqueous ammonium chloride (50 mL) and brine, dried over MgSO4, and concentrated in vacuo. The crude product was purified on a silica gel column (24 g) eluting with a 0-50% EtOAc gradient in hexanes to give the title compound as a clear, colorless oil (107 mg, 100%). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.27-1.35 (m, 9 H), 2.05 (d, J=12.6 Hz, 3 H), 2.20-2.28 (m, 3 H), 3.77-3.85 (m, 3 H), 4.52-4.68 (m, 1H), 6.59 (d, J=3.0 Hz, 1 H), 6.81-6.90 (m, 1 H), 7.68 (d, J=3.3 Hz, 1 H), 7.71 (d, J=8.8 Hz, 1 H); ESI-MS m/z [M+H]+ calc'd for C20H26N4O3, 371; found 371.

Aufarbeitung

  1. washwashed with saturated aqueous ammonium chloride (50 mL) and brine
  2. dry with materialdried over MgSO4
  3. concentrationconcentrated in vacuo
  4. customThe crude product was purified on a silica gel column (24 g)
  5. washeluting with a 0-50% EtOAc gradient in hexanes

Quellen und Nachweise

ORD-Eintrag
ord-6b4b05b5c12e4aa68f2b19634dfc2555
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08835420B2

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