Dichloromethane → 7-amino-4-(1,4-dioxaspiro[4.5]dec-7-en-8-yl)-2-methyl-2,3-dihydro-1H-isoindol-1-one

HRID 511247

Reaktionsgleichung

Reaktionsgleichung von HRID 511247
[NH2:1][C:2]1[CH:3]=[CH:4][C:5](Br)=[C:6]2[C:10]=1[C:9](=[O:11])[N:8]([CH3:12])[CH2:7]2.[O:14]1[C:18]2([CH2:23][CH2:22][C:21](B3OC(C)(C)C(C)(C)O3)=[CH:20][CH2:19]2)[O:17][CH2:16][CH2:15]1.C(=O)([O-])[O-].[K+].[K+].ClCCl>O1CCOCC1.O.C1C=CC(P([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C1C=CC(P([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl.[Fe]>[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([C:21]2[CH2:22][CH2:23][C:18]3([O:17][CH2:16][CH2:15][O:14]3)[CH2:19][CH:20]=2)=[C:6]2[C:10]=1[C:9](=[O:11])[N:8]([CH3:12])[CH2:7]2

Komponenten

8

Edukt 4

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 36970768-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1,4-dioxaspiro(4.5)dec-7-eneHCID 534084597-Amino-4-bromo-2-methylisoindolin-1-one

Produkt 1

HCID 672553637-amino-4-(1,4-dioxaspiro[4.5]dec-7-en-8-yl)-2-methyl-2,3-dihydro-1H-isoindol-1-one

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178477754HCID 178477754, VerbindungKatalysatorHCID 962WaterLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Versuchsvorschrift

A mixture of 7-amino-4-bromo-2-methyl-2,3-dihydro-1H-isoindol-1-one (1.7 g, 7.0 mmol), 1,4-dioxa-spiro[4,5]dec-7-en-8-boronic acid pinacol ester (2.2 g, 8.5 mmol) (preparation: WO 2007/141517), potassium carbonate (2.9 g, 21 mmol) and [1,1-bis(diphenylphosphino)ferrocene] dichloropalladium(II), complex with dichloromethane (1:1) (0.57 g, 0.69 mmol) in 1,4-dioxane (40 mL) and H2O (10 mL) was evacuated and refilled with nitrogen (3×) and irradiated in the microwave at 100° C. for 30 min. The reaction mixture was partitioned between EtOAc and brine and separated. The aqueous layer was extracted with EtOAc (3×) and the combined organic fractions were dried over sodium sulfate, filtered, and concentrated. The compound was purified on an Isco Combiflash eluting with 30 to 100% EtOAc in heptane to afford the title compound. 1H NMR (400 MHz, DMSO-d6) δ 7.14 (d, J=8.34 Hz, 1H), 6.55 (d, J=8.59 Hz, 1H), 6.08 (s, 2H), 5.60-5.66 (m, 1H), 4.39 (s, 2H), 3.91 (s, 4H), 2.98 (s, 3H), 2.50 (td, J=1.86, 3.60 Hz, 1H), 2.42-2.48 (m, 2H), 2.31-2.37 (m, 2H), 1.77 (t, J=6.44 Hz, 2H); MS (ES+): m/z: 302.1621 [MH+]. HPLC: tR=1.21 min (UPLC TOF MS: polar—3 min).

Aufarbeitung

  1. customwas evacuated
  2. additionrefilled with nitrogen (3×)
  3. customirradiated in the microwave at 100° C. for 30 min
  4. customThe reaction mixture was partitioned between EtOAc and brine
  5. customseparated
  6. extractionThe aqueous layer was extracted with EtOAc (3×)
  7. dry with materialthe combined organic fractions were dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe compound was purified on an Isco Combiflash
  11. washeluting with 30 to 100% EtOAc in heptane

Quellen und Nachweise

ORD-Eintrag
ord-fa91e1eb812e47d9bb045eedd9148f50
Quelldatensatz
uspto-grants-2015_08
Patentnummer
US09096624B2

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