Water → 2,4-Difluoro-N-[5-[4-(5-{[4-(1-methylethyl)-1-piperazinyl]methyl}-1,3-oxazol-2-yl)-1-(phenylsulfonyl)-1H-indazol-6-yl]-2-(methyloxy)-3-pyridinyl]benzenesulfonamide

HRID 2042374Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2042374
Cl[C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[N:7][N:8]2[S:11]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)(=[O:13])=[O:12])=[C:4]([C:20]2[O:21][C:22]([CH2:25][N:26]3[CH2:31][CH2:30][N:29]([CH:32]([CH3:34])[CH3:33])[CH2:28][CH2:27]3)=[CH:23][N:24]=2)[CH:3]=1.[F:35][C:36]1[CH:41]=[C:40]([F:42])[CH:39]=[CH:38][C:37]=1[S:43]([NH:46][C:47]1[C:48]([O:62][CH3:63])=[N:49][CH:50]=[C:51](B2OC(C)(C)C(C)(C)O2)[CH:52]=1)(=[O:45])=[O:44].[O-]P([O-])([O-])=O.[K+].[K+].[K+].O>O1CCOCC1.Cl[Pd]C1C=CC=CC=1C1C=CC=CC=1N(C)C.[C@H]12C[C@H](CC1)CC2PC1C[C@H]2C[C@@H]1CC2>[F:35][C:36]1[CH:41]=[C:40]([F:42])[CH:39]=[CH:38][C:37]=1[S:43]([NH:46][C:47]1[C:48]([O:62][CH3:63])=[N:49][CH:50]=[C:51]([C:2]2[CH:10]=[C:9]3[C:5]([CH:6]=[N:7][N:8]3[S:11]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)(=[O:12])=[O:13])=[C:4]([C:20]3[O:21][C:22]([CH2:25][N:26]4[CH2:27][CH2:28][N:29]([CH:32]([CH3:33])[CH3:34])[CH2:30][CH2:31]4)=[CH:23][N:24]=3)[CH:3]=2)[CH:52]=1)(=[O:45])=[O:44]

Komponenten

7

Edukt 4

HCID 962WaterHCID 62657Potassium Phosphate, TribasicHCID 595647052,4-difluoro-N-(2-methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl)benzenesulfonamideHCID 595647082-[1-(Benzenesulfonyl)-6-chloroindazol-4-yl]-5-[(4-propan-2-ylpiperazin-1-yl)methyl]-1,3-oxazole

Produkt 1

HCID 595647092,4-Difluoro-N-[5-[4-(5-{[4-(1-methylethyl)-1-piperazinyl]methyl}-1,3-oxazol-2-yl)-1-(phenylsulfonyl)-1H-indazol-6-yl]-2-(methyloxy)-3-pyridinyl]benzenesulfonamideAusbeute 26,5 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178420574HCID 178420574, VerbindungKatalysatorHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
120 °C

Versuchsvorschrift

To a solution of 6-chloro-4-(5-{[4-(1-methylethyl)-1-piperazinyl]methyl}-1,3-oxazol-2-yl)-1-(phenylsulfonyl)-1H-indazole (0.2 g, 0.40 mmol) and 2,4-difluoro-N-[2-(methoxy)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-pyridinyl]benzenesulfonamide (0.222 g, 0.52 mmol) in 1,4-dioxane (2 ml) was added chloro[2′-(dimethylamino)-2-biphenylyl]palladium-1(1R,4S)-bicyclo[2.2.1]hept-2-yl[(1S,4R)-bicyclo[2.2.1]hept-2-yl]phosphane (11.2 g, 0.020 mmol), potassium phosphate tribasic (0.255 g, 1.20 mmol) and water (0.2 ml). The reaction mixture was heated to 120° C. with stirring for 3 h under microwave irradiation then filtered through a silica SPE, eluting with methanol. The solvent was removed in vacuo and the residue partitioned between dichloromethane (5 ml) and water (5 ml). The layers were separated and the aqueous extracted with further dichloromethane (2×2 ml). The combined organics were concentrated under a stream of nitrogen and the residue purified using silica gel chromatography, eluting with 0-25% methanol in dichloromethane. The appropriate fractions were evaporated in vacuo to give the title compound as a brown solid (0.081 g).

Aufarbeitung

  1. filtrationthen filtered through a silica SPE
  2. washeluting with methanol
  3. customThe solvent was removed in vacuo
  4. customthe residue partitioned between dichloromethane (5 ml) and water (5 ml)
  5. customThe layers were separated
  6. extractionthe aqueous extracted with further dichloromethane (2×2 ml)
  7. concentrationThe combined organics were concentrated under a stream of nitrogen
  8. customthe residue purified
  9. washeluting with 0-25% methanol in dichloromethane
  10. customThe appropriate fractions were evaporated in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-3cd53dcb257b4fe5a953c0a04f21f6df
Quelldatensatz
uspto-grants-2013_11
Patentnummer
US08586583B2

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