Dichloromethane → 2-[2-(3,5-dimethoxyphenyl)ethyl]-6-[1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl]-5H-pyrrolo[2,3-b]pyrazine

HRID 1052252Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1052252
Br[C:2]1[N:22](S(C2C=CC=CC=2)(=O)=O)[C:5]2=[N:6][CH:7]=[C:8]([CH2:10][CH2:11][C:12]3[CH:17]=[C:16]([O:18][CH3:19])[CH:15]=[C:14]([O:20][CH3:21])[CH:13]=3)[N:9]=[C:4]2[CH:3]=1.ClCCl.[O:35]1[CH2:40][CH2:39][CH:38]([N:41]2[CH:45]=[C:44](B3OC(C)(C)C(C)(C)O3)[CH:43]=[N:42]2)[CH2:37][CH2:36]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].C(=O)([O-])[O-].[K+].[K+]>O.Cl[Pd]Cl.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].O1CCOCC1>[CH3:19][O:18][C:16]1[CH:17]=[C:12]([CH2:11][CH2:10][C:8]2[N:9]=[C:4]3[CH:3]=[C:2]([C:44]4[CH:43]=[N:42][N:41]([CH:38]5[CH2:39][CH2:40][O:35][CH2:36][CH2:37]5)[CH:45]=4)[NH:22][C:5]3=[N:6][CH:7]=2)[CH:13]=[C:14]([O:20][CH3:21])[CH:15]=1

Komponenten

9

Edukt 5

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 62657Potassium Phosphate, TribasicHCID 457884961-(Tetrahydro-2H-pyran-4-yl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 899637236-bromo-2-[2-(3,5-dimethoxyphenyl)ethyl]-5-(phenylsulfonyl)-5H-pyrrolo[2,3-b]pyrazine

Produkt 1

HCID 730562402-[2-(3,5-dimethoxyphenyl)ethyl]-6-[1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl]-5H-pyrrolo[2,3-b]pyrazineAusbeute 19,4 %

Reagenzien, Katalysatoren, Lösungsmittel 3

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

Reaktionsbedingungen

Temperatur
88 °C

Versuchsvorschrift

A stirred mixture of 6-bromo-2-[2-(3,5-dimethoxyphenyl)ethyl]-5-(phenylsulfonyl)-5H-pyrrolo[2,3-b]pyrazine (15.0 mg, 29.8 μmol), [1,1′-bis(diphenylphosphino)ferrocene]-dichloropalladium(II) complexed with dichloromethane (1:1) (1.30 mg, 1.59 μmol), 1-(tetrahydro-2H-pyran-4-yl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (8.9 mg, 32.0 μmol), and potassium phosphate (13.5 mg, 63.6 μmol) in water (0.2 mL)/1,4-dioxane (0.40 mL) was heated at 88° C. After 1 hour, the volatiles were removed under vacuum and the residues were dissolved in methanol (1 mL). Potassium carbonate (8.8 mg, 63.7 μmol) was added and the reaction mixture was then warmed up to 60° C. After 1 hour, the reaction mixture was cooled to ambient temperature and was purified on RP-HPLC (XBridge C18 column, eluting with a gradient of acetonitrile/water containing 0.05% TFA, at flow rate of 30 mL/min) to give the desired product (2.5 mg) as its TFA salt. LCMS calculated for C24H28N5O3 (M+H)+: m/z=434.2. Found: 434.2.

Aufarbeitung

  1. customthe volatiles were removed under vacuum
  2. dissolutionthe residues were dissolved in methanol (1 mL)
  3. temperaturethe reaction mixture was then warmed up to 60° C
  4. waitAfter 1 hour
  5. temperaturethe reaction mixture was cooled to ambient temperature
  6. customwas purified on RP-HPLC (XBridge C18 column
  7. washeluting with a gradient of acetonitrile/water containing 0.05% TFA, at flow rate of 30 mL/min)

Quellen und Nachweise

ORD-Eintrag
ord-9119fed60c0e4933a3edb4fe29b1b3b6
Quelldatensatz
uspto-grants-2016_07
Patentnummer
US09388185B2

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