Dimethylamine → 7-amino-4-[4-(dimethylamino)cyclohexyl]-2-methyl-2,3-dihydro-1H-isoindol-1-one

HRID 511483Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 511483
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([CH:13]2[CH2:18][CH2:17][C:16](=O)[CH2:15][CH2:14]2)=[C:6]2[C:10]=1[C:9](=[O:11])[N:8]([CH3:12])[CH2:7]2.[CH3:20][NH:21][CH3:22].C1COCC1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([CH:13]2[CH2:18][CH2:17][CH:16]([N:21]([CH3:22])[CH3:20])[CH2:15][CH2:14]2)=[C:6]2[C:10]=1[C:9](=[O:11])[N:8]([CH3:12])[CH2:7]2

Komponenten

6

Edukt 4

HCID 674DimethylamineHCID 8028TetrahydrofuranHCID 5049666Sodium triacetoxyborohydrideHCID 672561257-amino-2-methyl-4-(4-oxocyclohexyl)-2,3-dihydro-1H-isoindol-1-one

Produkt 1

HCID 672542857-amino-4-[4-(dimethylamino)cyclohexyl]-2-methyl-2,3-dihydro-1H-isoindol-1-oneAusbeute 58 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 111,2-DichloroethaneLösungsmittel

Versuchsvorschrift

A solution of 7-amino-2-methyl-4-(4-oxocyclohexyl)-2,3-dihydro-1H-isoindol-1-one (100.0 mg, 0.3871 mmol) in 1,2-Dichloroethane (2.0 mL) was charged with 2.0 M of dimethylamine in THF (0.2903 mL, 0.5807 mmol) and sodium triacetoxyborohydride (164.1 mg, 0.7743 mmol). The reaction mixture was stirred at rt for 24 hours. The reaction mixture was quenched with NaHCO3 (10 mL) and extracted with EtOAc (20 mL). The organic layer was washed with brine (10 mL), dried over Na2SO4, filtered and concentrated under reduced pressure to yield a light yellow oil. The crude material was purified by silica gel chromatography on the combi-flash Rf system using DCM/7M NH3 in MeOH (100:0→90:10) as eluent. The fractions containing product were combined and concentrated under reduced pressure to yield a light yellow solid, 64.7 mg (58% yield). 1H NMR (CDCl3, 400 MHz): δ=1.53 (d, J=11.12 Hz, 4 H), 1.91 (d, J=11.12 Hz, 2 H), 2.08 (d, J=14.65 Hz, 2 H), 2.31 (br. s., 6 H), 2.45 (br. s., 1 H), 2.48-2.58 (m, 1 H), 3.14 (s, 3 H), 4.30 (s, 2 H), 5.07 (br. s., 2 H), 6.57 (d, J=8.34 Hz, 1 H), 7.26 (br. s., 1 H). MS (ES+): m/z 288.21 [MH+] (TOF, polar).

Aufarbeitung

  1. customThe reaction mixture was quenched with NaHCO3 (10 mL)
  2. extractionextracted with EtOAc (20 mL)
  3. washThe organic layer was washed with brine (10 mL)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customto yield a light yellow oil
  8. customThe crude material was purified by silica gel chromatography on the combi-flash Rf system
  9. additionThe fractions containing product
  10. concentrationconcentrated under reduced pressure
  11. customto yield a light yellow solid, 64.7 mg (58% yield)

Quellen und Nachweise

ORD-Eintrag
ord-65a8dcad25fe475b83ad5e87b5752de4
Quelldatensatz
uspto-grants-2015_08
Patentnummer
US09096624B2

Notizen zur Reaktion

Wird geladen…