Sodium Carbonate → 2-Methyl-N-[6-(2-oxo-2,3-dihydro-1H-indol-4-yl)-1H-indazol-4-yl]-1,3-thiazole-4-carboxamide

HRID 520650Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 520650
Br[C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[C:5](Cl)[NH:6]2.[CH3:12][C:13]1[S:14][CH:15]=[C:16]([C:18]([NH:20][C:21]2[C:22]3[C:26]([CH:27]=[C:28](B4OC(C)(C)CC(C)(C)O4)[CH:29]=2)=[N:25][N:24](C2CCCCO2)[CH:23]=3)=[O:19])[N:17]=1.C(=O)([O-])[O-:47].[Na+].[Na+].O1CCOCC1>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].O>[CH3:12][C:13]1[S:14][CH:15]=[C:16]([C:18]([NH:20][C:21]2[CH:29]=[C:28]([C:2]3[CH:10]=[CH:9][CH:8]=[C:7]4[C:3]=3[CH2:4][C:5](=[O:47])[NH:6]4)[CH:27]=[C:26]3[C:22]=2[CH:23]=[N:24][NH:25]3)=[O:19])[N:17]=1

Komponenten

7

Edukt 4

HCID 10340Sodium CarbonateHCID 312751,4-DioxaneHCID 197003094-bromo-2-chloro-1H-indoleHCID 582558332-Methyl-N-[2-(tetrahydro-2H-pyran-2-yl)-6-(4,4,6,6-tetramethyl-1,3,2-dioxaborinan-2-yl)-2H-indazol-4-yl]-1,3-thiazole-4-carboxamide

Produkt 1

HCID 532332132-Methyl-N-[6-(2-oxo-2,3-dihydro-1H-indol-4-yl)-1H-indazol-4-yl]-1,3-thiazole-4-carboxamide

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)KatalysatorHCID 962WaterLösungsmittel

Reaktionsbedingungen

Temperatur
140 °C

Versuchsvorschrift

4-Bromo-2-chloro-1H-indole (24 mg), 2-methyl-N-[2-(tetrahydro-2H-pyran-2-yl)-6-(4,4,6,6-tetramethyl-1,3,2-dioxaborinan-2-yl)-2H-indazol-4-yl]-1,3-thiazole-4-carboxamide (50 mg), Pd(dppf)Cl2 (8 mg) and sodium carbonate (44 mg) were added to a microwave vial. 1,4-Dioxane (0.5 ml) and water (0.5 ml) were added and the reaction was heated in the microwave at 140° C. for 20 min. The reaction was passed through a 1 g silica cartridge washing with DCM:methanol. The solvent was evaporated in the blow down. The residue was dissolved in DMSO:methanol (1.6 ml, 1:1, v/v), passed through a C18 cartridge (1 g) washing with acetonitrile and evaporated in the blow down. The residue was dissolved in DMSO:methanol (1.6 ml, 1:1, v/v) and purified by MDAP (method M). The pure fraction was evaporated to dryness to give title compound, 8 mg.

Aufarbeitung

  1. washwashing with DCM
  2. customThe solvent was evaporated in the blow down
  3. dissolutionThe residue was dissolved in DMSO
  4. washwashing with acetonitrile
  5. customevaporated in the blow down
  6. dissolutionThe residue was dissolved in DMSO
  7. custommethanol (1.6 ml, 1:1, v/v) and purified by MDAP (method M)
  8. customThe pure fraction was evaporated to dryness

Quellen und Nachweise

ORD-Eintrag
ord-4a0e8f73252242b0b3255c51df8f760e
Quelldatensatz
uspto-grants-2016_05
Patentnummer
US09326987B2

Notizen zur Reaktion

Wird geladen…