Hydrochloric Acid → 5-(4-(2-Amino-2-oxoethyl)phenyl)-6-chloro-1H-indazole-3-carboxylic acid

HRID 1054829Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1054829
Br[C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([NH2:11])=[O:10])=[CH:4][CH:3]=1.CC1(C)COB(B2OCC(C)(C)CO2)OC1.C([O-])(=O)C.[K+].Br[C:34]1[CH:35]=[C:36]2[C:40](=[CH:41][C:42]=1[Cl:43])[NH:39][N:38]=[C:37]2[C:44]([OH:46])=[O:45].C(=O)([O-])[O-].[K+].[K+].Cl>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.CCO>[NH2:11][C:9](=[O:10])[CH2:8][C:5]1[CH:6]=[CH:7][C:2]([C:34]2[CH:35]=[C:36]3[C:40](=[CH:41][C:42]=2[Cl:43])[NH:39][N:38]=[C:37]3[C:44]([OH:46])=[O:45])=[CH:3][CH:4]=1

Komponenten

11

Edukt 6

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 2569512-(4-Bromophenyl)acetamideHCID 517044Potassium AcetateHCID 2734316Bis(neopentyl glycolato)diboronHCID 866987915-bromo-6-chloro-1H-indazole-3-carboxylic acid

Produkt 1

HCID 866988215-(4-(2-Amino-2-oxoethyl)phenyl)-6-chloro-1H-indazole-3-carboxylic acidAusbeute 3 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)Katalysator2×HCID 702EthanolLösungsmittelHCID 962WaterLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
130 °C

Versuchsvorschrift

A suspension of 2-(4-bromophenyl)acetamide (85.0 mg, 0.37 mmol), 5,5,5′,5′-tetramethyl-2,2′-bi-1,3,2-dioxaborinane (136 mg, 0.37 mmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (15.0 mg, 0.018 mmol) and potassium acetate (107 mg, 1.09 mmol) in 1,4-dioxane (1 mL) was sealed in a pressure tube and heated to 130° C. for 1 hour. To the mixture was added 5-bromo-6-chloro-1H-indazole-3-carboxylic acid (100 mg, 0.36 mmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (14.7 mg, 0.018 mmol), 2 N aqueous potassium carbonate solution (0.5 mL, 1 mmol) and EtOH (2 mL). The mixture was sealed and heated to 130° C. for 1 hour. Water (3 mL) was added to the reaction mixture, followed by 1 N HCl solution to adjust the pH to 2. The layers were separated and the aqueous layer was extracted with EtOAc (3×5 mL). The combined organic layers were dried over Na2SO4 and concentrated in vacuo. The crude material was purified by reverse phase HPLC (Column: Waters Sunfire C18 19×100 mm, 5 μm; Mobile phase A: 0.05% TFA in water (v/v); Mobile phase B: 0.05% TFA in MeCN (v/v); 95.0% H2O/5.0% MeCN linear to 0% H2O/100% MeCN in 10.5 min, HOLD at 0% H2O/100% MeCN to 12.0 min. Flow: 25 mL/min) to afford the title compound (3.3 mg, 3% yield). MS (ES+) 330.1 (M+H)+. Retention time=2.04 minutes (Column: Waters Atlantis dC18 4.6×50 mm, 5 μm; Mobile phase A: 0.05% TFA in water (v/v); Mobile phase B: 0.05% TFA in MeCN (v/v); Gradient: 95:5 A:B linear to 5:95 A:B in 4.0 min, hold at 5:95 A:B to 5.0 min. Flow: 2 mL/min).

Aufarbeitung

  1. customwas sealed in a pressure tube
  2. customThe mixture was sealed
  3. temperatureheated to 130° C. for 1 hour
  4. customThe layers were separated
  5. extractionthe aqueous layer was extracted with EtOAc (3×5 mL)
  6. dry with materialThe combined organic layers were dried over Na2SO4
  7. concentrationconcentrated in vacuo
  8. customThe crude material was purified by reverse phase HPLC (Column: Waters Sunfire C18 19×100 mm, 5 μm; Mobile phase A: 0.05% TFA in water (v/v); Mobile phase B: 0.05% TFA in MeCN (v/v); 95.0% H2O/5.0% MeCN linear to 0% H2O/100% MeCN in 10.5 min, HOLD at 0% H2O/100% MeCN to 12.0 min. Flow: 25 mL/min)

Quellen und Nachweise

ORD-Eintrag
ord-a68086f5f50e44cd8c9630bb8871458b
Quelldatensatz
uspto-grants-2016_07
Patentnummer
US09394285B2

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