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]] → HCID 131728193, compound

HRID 18865Notes

Reaction equation

HRID 18865 reaction equation
[CH2:1]([O:46][C:47]1([C:80]2[CH:85]=[CH:84][CH:83]=[CH:82][C:81]=2[C:86]#[CH:87])[C@H:51]2[C@H:52](O[Si](C(C)(C)C)(C)C)[N:53](C(OCC(Cl)(Cl)Cl)=O)[C:54]3[CH:61]=[CH:60][C:59]([O:62][CH3:63])=[CH:58][C:55]=3[C:56](=[O:57])[N:50]2[CH:49]=[CH:48]1)[CH2:2][CH2:3][O:4][C:5]1([C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][C:39]=2[C:44]#[CH:45])[C@H:9]2[C@H:10](O[Si](C(C)(C)C)(C)C)[N:11](C(OCC(Cl)(Cl)Cl)=O)[C:12]3[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][C:13]=3[C:14](=[O:15])[N:8]2[CH:7]=[CH:6]1>C1COCC1>[CH2:3]([O:4][C:5]1([C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][C:39]=2[C:44]#[CH:45])[C@@H:9]2[CH:10]=[N:11][C:12]3[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][C:13]=3[C:14](=[O:15])[N:8]2[CH:7]=[CH:6]1)[CH2:2][CH2:1][O:46][C:47]1([C:80]2[CH:85]=[CH:84][CH:83]=[CH:82][C:81]=2[C:86]#[CH:87])[C@@H:51]2[CH:52]=[N:53][C:54]3[CH:61]=[CH:60][C:59]([O:62][CH3:63])=[CH:58][C:55]=3[C:56](=[O:57])[N:50]2[CH:49]=[CH:48]1

Participants

3

Reactant 1

HCID 1317281921,1'-[[(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]]

Product 1

HCID 131728193HCID 131728193, compoundYield 38%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

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).

Workup

  1. stirringto stir for 45 min when TLC
  2. customthe complete consumption of the starting material
  3. filtrationThe solids were filtered
  4. washrinsed with H2O and CHCl3
  5. extractionThe aqueous layer was extracted with CHCl3 (3×25 mL)
  6. washwashed with H2O (50 mL), brine (50 mL)
  7. dry with materialdried (MgSO4)
  8. filtrationFiltration and evaporation of solvent
  9. customafforded the crude product which
  10. customwas purified by flash column chromatography (99.8:0.2 v/v CHCl3/MeOH

Sources & evidence

ORD record
ord-bf820d3363ef4497b4afdf1430a37671
Source dataset
uspto-grants-2010_06
Patent number
US07741319B2

Reaction notes

Loading…