1,8-Diazabicyclo(5.4.0)undec-7-ene → HCID 91531190, compound

HRID 2389492Notes

Reaction equation

HRID 2389492 reaction equation
[SH:1][C:2]1[N:6]([CH2:7][C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[C:5]2[CH:15]=[CH:16][CH:17]=[CH:18][C:4]=2[N:3]=1.C1CCN2C(=NCCC2)CC1.[C:30]([O:34][C:35](=[O:41])[NH:36][CH2:37][CH2:38][CH2:39]Br)([CH3:33])([CH3:32])[CH3:31].CCN(C(C)C)C(C)C.C1C=CC(C(Cl)(C2C(Cl)=CC=CC=2)C2C=CC=CC=2)=CC=1>C1COCC1>[C:11]([O:10][C:8](=[O:9])[CH2:7][N:6]1[C:5]2[CH:15]=[CH:16][CH:17]=[CH:18][C:4]=2[N:3]=[C:2]1[S:1][CH2:39][CH2:38][CH2:37][NH:36][C:35]([O:34][C:30]([CH3:31])([CH3:33])[CH3:32])=[O:41])([CH3:13])([CH3:14])[CH3:12]

Participants

7

Reactant 5

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 81531DiisopropylethylamineHCID 945242-Chlorotrityl chlorideHCID 4460490tert-butyl N-(3-bromopropyl)carbamateHCID 178451223HCID 178451223, compound

Product 1

HCID 91531190HCID 91531190, compoundYield 81.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent4×

Procedure

A solution of tert-butyl (2-mercapto-benzoimidazol-1-yl)-acetate (Intermediate 3-I, 502 mg, 1.9 mmol) and DBU (289 mg, 284 μl, 1.9 mmol) in THF (1 ml) is added onto a solution of (3-bromo-propyl)-carbamic acid tert-butyl ester (407 mg, 1.71 mmol) in THF (1 ml). The resulting solution is stirred at rt for 2 h. It becomes slowly turbid and the undesired solid is filtered on a fritted funnel. The solution is diluted with THF (2 ml) and DIPEA (491 mg, 650 μl, 3.8 mmol) is added. The mixture is poured onto a suspension of 2-chlorotrityl chloride resin (200-400 mesh), 1% DVB (1.0-1.6 mmol/g, 475 mg, 0.76 mmol) in THF (1 ml) and allowed to stir for 3 h. The resin is filtered and rinsed with THF. The solvent is removed in vacuo and the residue diluted with dichloromethane (5 ml). This organic phase is washed with an aqueous citric acid solution (pH=4) and with water. The solvent is evaporated under reduced pressure. The same purification process is repeated using dichloromethane instead of THF as the solvent. The obtained organic phase is washed with a saturated aqueous KH2PO4 solution and water. Evaporation of the solvent in vacuo affords a residue that is purified by flash chromatography on silica-gel (AcOEt/heptane, 1:2), yielding the title compound (587 mg) in 73% as a colourless oil: tR=2.41 min (LC-2), ESI-MS (pos.): m/z 422.50 [M+H]+; 1H-NMR (CDCl3): δ (ppm) 1.37 (s, 9H, tBu), 1.39 (s, 9H, tBu), 1.74 (quint. 2H, CH2CH2N), 3.20 (dd, 2H), 3.38 (t, 2H), 4.67 (s, 2H, CH2CO2), 5.82 (br. s, 1H, NH), 7.10-7.29 (m, 3Harom), 7.65 (m, 1Harom).

Workup

  1. filtrationthe undesired solid is filtered on a fritted funnel
  2. additionis added
  3. stirringto stir for 3 h
  4. filtrationThe resin is filtered
  5. washrinsed with THF
  6. customThe solvent is removed in vacuo
  7. additionthe residue diluted with dichloromethane (5 ml)
  8. washThis organic phase is washed with an aqueous citric acid solution (pH=4) and with water
  9. customThe solvent is evaporated under reduced pressure
  10. washThe obtained organic phase is washed with a saturated aqueous KH2PO4 solution and water
  11. customEvaporation of the solvent in vacuo
  12. customaffords a residue that
  13. customis purified by flash chromatography on silica-gel (AcOEt/heptane, 1:2)

Sources & evidence

ORD record
ord-1a25cb8ed9fd498bba402869a387e853
Source dataset
uspto-grants-2012_09
Patent number
US08273740B2

Reaction notes

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