Hydrogen Peroxide → HCID 178503810, compound

HRID 1508050Notes

Reaction equation

HRID 1508050 reaction equation
[CH3:1][C:2]1([CH3:33])[CH2:7][CH2:6][C:5]([C:8]2[CH:13]=[C:12]([C:14]([CH3:22])([N:16]3C[CH2:20][S:19][CH2:18][CH2:17]3)[CH3:15])[CH:11]=[CH:10][C:9]=2[NH:23][C:24]([C:26]2[NH:27][CH:28]=[C:29]([C:31]#[N:32])[N:30]=2)=[O:25])=[CH:4][CH2:3]1.OO.CCOC(C)=O>C(Cl)Cl.CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-]>[CH3:1][C:2]1([CH3:33])[CH2:7][CH2:6][C:5]([C:8]2[CH:13]=[C:12]([C:14]([CH3:15])([NH:16][CH2:17][CH2:18][S:19][CH3:20])[CH3:22])[CH:11]=[CH:10][C:9]=2[NH:23][C:24]([C:26]2[NH:27][CH:28]=[C:29]([C:31]#[N:32])[N:30]=2)=[O:25])=[CH:4][CH2:3]1

Participants

6

Reactant 3

HCID 784Hydrogen PeroxideHCID 8857Ethyl AcetateHCID 178424517HCID 178424517, compound

Product 1

HCID 178503810HCID 178503810, compoundYield 89.1%

Reagents, catalysts & solvents 2

HCID 11026Titanium isopropoxideCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 4-cyano-1H-imidazole-2-carboxylic acid [2-(4,4-dimethyl-cyclohex-1-enyl)-4-(1-methyl-1-thiomorpholin-4-yl-ethyl)-phenyl]-amide (as prepared in Example 14, step (e), 38.0 mg, 0.0820 mmol) in 0.5 mL of DCM at RT was added titanium (IV) isopropoxide (24.0 μL, 0.0820 mmol). The mixture was cooled to 0° C. and H2O2 (18 μL, 0.16 mmol, 30 wt % in H2O) was added. After stirring at 0° C. for 0.5 h and at −20° C. for 16 h, the mixture was treated with EtOAc (50 mL) and washed with H2O (2×10 mL) and brine (10 mL). The organic layer was dried over Na2SO4 and concentrated in vacuo. The residue was purified by silica gel chromatography (15-25% EtOAc/DCM) to afford the title compound (33 mg, 80%) as a white solid. 1H-NMR (CD3OD; 400 MHz): δ 8.16 (d, 1H, J=8.6 Hz), 7.99 (s, 1H), 7.49 (dd, 1H, J=8.6, 2.3 Hz), 7.37 (d, 1H, J=2.3 Hz), 5.74 (m, 1H), 2.91-3.07 (m, 8H), 2.31 (m, 2H), 2.08 (m, 2H), 1.60 (t, 2H, J=6.3 Hz), 1.42 (s, 6H), 1.09 (s, 6H). Mass spectrum (ESI-neg, m/z): Calcd. for C26H33N5O3S, 494.2 (M−H). found 494.2.

Workup

  1. washwashed with H2O (2×10 mL) and brine (10 mL)
  2. dry with materialThe organic layer was dried over Na2SO4
  3. concentrationconcentrated in vacuo
  4. customThe residue was purified by silica gel chromatography (15-25% EtOAc/DCM)

Sources & evidence

ORD record
ord-64be15a8dd6441abb31ecbdf27b03d7b
Source dataset
uspto-grants-2015_12
Patent number
US09221797B2

Reaction notes

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