2,6-Dimethylphenol → HCID 86674669, compound

HRID 1500597Notes

Reaction equation

HRID 1500597 reaction equation
Cl[CH2:2]C1C=C(C=CC=1OC)C=O.CC1C=CC=C(C)C=1O.C([O-])([O-])=O.[K+].[K+].[NH2:28][C:29]1[CH:43]=[CH:42][CH:41]=[CH:40][C:30]=1[C:31]([NH:33][CH2:34][C:35]1[O:36][CH:37]=[CH:38][CH:39]=1)=[O:32].FC(F)(F)S([O-])(=O)=O.[Yb+3].FC(F)(F)S([O-])(=O)=O.FC(F)(F)S([O-])(=O)=O>C(#N)C.CCO>[O:36]1[CH:37]=[CH:38][CH:39]=[C:35]1[CH2:34][N:33]1[C:31](=[O:32])[C:30]2[C:29](=[CH:43][CH:42]=[CH:41][CH:40]=2)[NH:28][CH2:2]1

Participants

8

Reactant 5

HCID 113352,6-DimethylphenolHCID 11430Potassium CarbonateHCID 104237Benzaldehyde, 3-(chloromethyl)-4-methoxy-HCID 8412692-amino-N-(furan-2-ylmethyl)benzamideHCID 2733225Ytterbium triflate

Product 1

HCID 86674669HCID 86674669, compoundYield 55,409.602%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
150 °C

Procedure

To a solution of 3-(chloromethyl)-4-methoxybenzaldehyde (85 mg, 0.46 mmol, 1.0 equiv) and 2,6-dimethylphenol (62 mg, 0.51 mmol, 1.1 equiv) in 3.0 mL of anhydrous acetonitrile, we added K2CO3 (320 mg, 2.3 mmol, 5.0 eq). The mixture was heated in a microwave reactor for 30 min at 150° C. After filtering off the solid and removing the solvent, 2-amino-N-(furan-2-ylmethyl)benzamide (110 mg, 0.51 umol, 1.1 equiv) in 5 mL of EtOH was added followed by addition of Ytterbium trifluoromethanesulfonate (57 mg, 0.02 umol, 0.2 equiv). The mixture was heated at 80° C. for 2 hours. The product was isolated via preparative HPLC purification and solvent was removed via reduced pressure lyophilization to give 2434(2,6-dimethylphenoxy)methyl)-4-methoxyphenyl)-3-(furan-2-ylmethyl)-2,3-dihydroquinazolin-4(1H)-one (64.5 mg, 30%) as a white solid after triturating with diethyl ether. 1HNMR (400 MHz, DMSO-d6) δ ppm 2.16 (s, 6H), 3.77 (s, 3 H), 3.86 (d, J=15.6 Hz, 1 H), 4.69 (d, J=1.9 Hz, 2 H), 5.19 (d, J=15.4 Hz, 1 H), 5.75 (d, J=2.3, Hz, 1 H), 6.30 (d, J=3.2 Hz, 1 H), 6.39 (dd, J=3.2, 1.9 Hz, 1 H), 6.62-6.70 (m, 2 H), 6.86-6.97 (m, 1 H), 6.99-7.04 (m, 3 H), 7.19-7.29 (m, 2 H), 7.32 (d, J=2.3 Hz, 1 H), 7.49 (d, J=2.4, Hz, 1 H), 7.57 (dd, J=1.8, 0.7 Hz, 1 H), 7.68 (dd, J=7.9, 1.5 Hz, 1 H); HPLC: tR=6.88 min, UV254=97%; HRMS (ESI): m/z calculated for C29H28N2O4 [M+1]+469.2132, found 469.2138.

Workup

  1. filtrationAfter filtering off the solid
  2. additionwas added
  3. temperatureThe mixture was heated at 80° C. for 2 hours
  4. customThe product was isolated via preparative HPLC purification and solvent
  5. customwas removed via reduced pressure lyophilization

Sources & evidence

ORD record
ord-3b44a57db15b47e98bb60dc368d6d8b4
Source dataset
uspto-grants-2015_12
Patent number
US09206154B2

Reaction notes

Loading…