1-Methylpiperazine → HCID 178480928, Verbindung

HRID 511249Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 511249
[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][N:21]1[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([C@H:13]2[CH2:18][CH2:17][C@H:16]([N:24]3[CH2:25][CH2:26][N:21]([CH3:20])[CH2:22][CH2:23]3)[CH2:15][CH2:14]2)=[C:6]2[C:10]=1[C:9](=[O:11])[N:8]([CH3:12])[CH2:7]2

Komponenten

5

Edukt 3

HCID 531671-MethylpiperazineHCID 5049666Sodium triacetoxyborohydrideHCID 672561257-amino-2-methyl-4-(4-oxocyclohexyl)-2,3-dihydro-1H-isoindol-1-one

Produkt 1

HCID 178480928HCID 178480928, Verbindung

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 1-methylpiperazine (58.16 mg, 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 and by silica gel chromatography on the combi-flash Rf system using DCM/7M NH3 in MeOH (100:0→90:10) as eluent to afford the cis isomer (76.5 mg, 58%, first eluting product) and the trans isomer (30.0 mg, 23%, second eluting product). Cis isomer: 1H NMR (CDCl3, 400 MHz): δ=1.42-1.56 (m, 4 H), 1.82-1.96 (m, 2 H), 2.06 (d, J=11.87 Hz, 2 H), 2.27 (br. s., 1 H), 2.34 (s, 3 H), 2.38-2.78 (m, 9 H), 3.14 (s, 3 H), 4.31 (s, 2 H), 5.08 (s, 2 H), 6.58 (d, J=8.34 Hz, 1 H), 7.18 (d, J=8.34 Hz, 1 H). MS (ES+): m/z 343.25 [MH+]. Trans isomer: 1H NMR (CDCl3, 400 MHz): δ=1.35-1.75 (m, 7 H), 1.91 (d, J=12.13 Hz, 2 H), 2.03-2.13 (m, 2 H), 2.34 (s, 3 H), 2.47-2.82 (m, 7 H), 3.14 (s, 3 H), 4.28 (s, 2 H), 5.09 (s, 2 H), 6.56 (d, J=8.34 Hz, 1 H), 7.09 (d, J=8.34 Hz, 1 H). MS (ES+): m/z 343.26 [MH+].

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 and by silica gel chromatography on the combi-flash Rf system
  9. customto afford the cis isomer (76.5 mg, 58%, first eluting product)

Quellen und Nachweise

ORD-Eintrag
ord-205a7a5781f24176abd4a795644df55f
Quelldatensatz
uspto-grants-2015_08
Patentnummer
US09096624B2

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