Cesium carbonate → 1-(2,2,2-trifluoroethyl)4-(2,4,6-trimethoxybenzyl)-3,4-dihydro-1H-1,4benzodiazepine-2,5-dione

HRID 2213339Notes

Reaction equation

[CH3:1][O:2][C:3]1[CH:22]=[C:21]([O:23][CH3:24])[CH:20]=[C:19]([O:25][CH3:26])[C:4]=1[CH2:5][N:6]1[C:12](=[O:13])[C:11]2[CH:14]=[CH:15][CH:16]=[CH:17][C:10]=2[NH:9][C:8](=[O:18])[CH2:7]1.C(=O)([O-])[O-].[Cs+].[Cs+].[F:33][C:34]([F:38])([F:37])[CH2:35]I>CN(C=O)C.C(OCC)(=O)C.O>[F:33][C:34]([F:38])([F:37])[CH2:35][N:9]1[C:10]2[CH:17]=[CH:16][CH:15]=[CH:14][C:11]=2[C:12](=[O:13])[N:6]([CH2:5][C:4]2[C:19]([O:25][CH3:26])=[CH:20][C:21]([O:23][CH3:24])=[CH:22][C:3]=2[O:2][CH3:1])[CH2:7][C:8]1=[O:18]

Participants

Conditions

Temperature: 55 °C

Procedure

The product from Step 4B (6 g, 0.017 mol) was dissolved in DMF (40 ml) at room temperature under nitrogen. Caesium carbonate (8.2 g, 0.025 mol) was added followed by trifluoroethyl iodide (8.8 g, 0.025 mol) and the mixture stirred at 55° C. for 16 hr. The reaction mixture was taken up in ethyl acetate/water, the organic layer washed (water, brine), dried (MgSO4) and evaporated in vacuo. Purification by chromatography (SiO2, ethyl acetate/dichloromethane) afforded the product as a white solid (2.6 g, 35%). (1H NMR, CDCl3) δ 3.68–3.83 (11H, m), 4.13–4.17 (1H, m), 4.72 (1H, S d, J=13.6 Hz), 4.84–4.88 (1H, m) 5.04 (1H, d, J=13.6Hz), 6.13 (2H, s), 7.18 (1H, d, J=8.3 Hz), 7.32–7.50 (2H, m), 7.96 (1H, m).

Workup

washthe organic layer washed (water, brine)
dry with materialdried (MgSO4)
customevaporated in vacuo
customPurification by chromatography (SiO2, ethyl acetate/dichloromethane)

Sources & evidence

ORD record: ord-032bad5c91e445c3b505eef972d7a1f4
Source dataset: uspto-grants-2006_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07105509B2

Reaction notes

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