Reaktion #47143

Reaktionsgleichung

17

1,1′-[[(Propane-1,3-diyl)dioxy]bis[(11S,11aS)-10-(2,2,2-trichloroethoxycarbonyl)-11-(tert-butyldimethylsilyloxy)-7-methoxy-2-ethynylphenyl-1,10,11,11a-tetrahydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-5-one]]

→

glass

Ausbeute 38.0%

1,1′-[[(Propane-1,3-diyl)dioxy]bis[(11aS)-7-methoxy-2-ethynylphenyl-1,11a-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-5-one]]

Ausbeute 38.0%

Lösungsmittel

THF

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.STIRRINGto stir for 45 min when TLC
2. 2
   Sonstigethe complete consumption of the starting material
3. 3
   FiltrationThe solids were filtered
4. 4
   Waschenrinsed with H2O and CHCl3
5. 5
   ExtraktionThe aqueous layer was extracted with CHCl3 (3×25 mL)
6. 6
   Waschenwashed with H2O (50 mL), brine (50 mL)
7. 7
   Trocknendried (MgSO4)
8. 8
   FiltrationFiltration and evaporation of solvent
9. 9
   Sonstigeafforded the crude product which
10. 10
    Sonstigewas purified by flash column chromatography (99.8:0.2 v/v CHCl3/MeOH

Vorschrift

10% Cd/Pd couple (314 mg, 2.55 mmol, 20 eq) was added to a rapidly stirring mixture of 17 (162 mg, 0.13 mmol), THF (4 mL) and 1 N NH4OAc (4 mL). The reaction mixture was allowed to stir for 45 min when TLC showed the complete consumption of the starting material. The solids were filtered and rinsed with H2O and CHCl3. The aqueous layer was extracted with CHCl3 (3×25 mL) and the organic extracts were combined, washed with H2O (50 mL), brine (50 mL) and dried (MgSO4). Filtration and evaporation of solvent afforded the crude product which was purified by flash column chromatography (99.8:0.2 v/v CHCl3/MeOH then gradient to 97.5:2.5 v/v CHCl3/MeOH) to afford ZC-209 as a yellow glass (33 mg, 38%): 1H NMR (400 MHz, CDCl3) δ 7.79 (d, 2H, J=3.9 Hz, H11), 7.42 (s, 2H, H6), 7.39-7.37 (m, 4H, H15), 7.26-7.19 (m, 8H, H3, H16 and H17), 6.78 (s, 2H, H9), 4.30-4.19 (m, 6H, OCH2CH2CH2O and H11a), 3.86 (s, 6H, OCH3×2), 3.36 (dd, 2H, J=11.7, 16.4 Hz, H1), 3.18 (dd, 2H, J=5.4, 16.4 Hz, H1), 2.37-2.34 (m, 2H, OCH2CH2CH2O); 13C NMR (100.6 MHz, CDCl3) δ 162.0 (C11), 161.3 (Cquat), 151.4 (Cquat), 148.2 (Cquat), 140.3 (Cquat), 132.8 (C3), 131.4 (C15), 128.4 (C16 and C17), 122.9 (Cquat), 118.7 (Cquat), 112.0 (C6), 111.2 (C9), 105.1 (Cquat), 94.3 (Calkyne), 83.3 (Calkyne), 65.5 (OCH2CH2CH2O), 56.2 (OCH3), 53.8 (C11a), 37.9 (C1), 28.8 (OCH2CH2CH2O); MS (ES), m/z (relative intensity) 729 (M+., 100).

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