Imidazole → HCID 25235224, compound

HRID 453057Notes

Reaction equation

HRID 453057 reaction equation
[NH2:1][C:2]1[C:10]([C:11]([F:14])([F:13])[F:12])=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=O.N1[CH:19]=[CH:18]N=C1.C(Cl)(=O)C.Cl.[NH2:25][CH:26]1[CH2:31][CH2:30][C:29](=[O:32])[NH:28][C:27]1=[O:33].P(OC1C=CC=CC=1)(OC1C=CC=CC=1)OC1C=CC=CC=1>C(#N)C.O>[CH3:18][C:19]1[N:25]([CH:26]2[CH2:31][CH2:30][C:29](=[O:32])[NH:28][C:27]2=[O:33])[C:4](=[O:6])[C:3]2[C:2](=[C:10]([C:11]([F:14])([F:13])[F:12])[CH:9]=[CH:8][CH:7]=2)[N:1]=1

Participants

8

Reactant 5

HCID 795Imidazole2×HCID 6367Acetyl chlorideHCID 7540Triphenyl phosphiteHCID 1345483-Aminopiperidine-2,6-dione hydrochlorideHCID 6045692-Amino-3-(trifluoromethyl)benzoic acid

Product 1

HCID 25235224HCID 25235224, compoundYield 10%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

To a stirred mixture of 2-amino-3-(trifluoromethyl)benzoic acid (2.0 g, 9.8 mmol) and imidazole (0.8 g, 12 mmol) in acetonitrile (20 mL), was added acetyl chloride (0.83 mL, 12 mmol) at room temperature. The mixture was stirred at room temperature overnight. To the mixture, was added 3-amino-piperidine-2,6-dione hydrogen chloride (1.6 g, 9.8 mmol), imidazole (1.5 g, 22 mmol) and triphenyl phosphite (3.1 mL, 12 mmol) and heated to reflux for 22 hours. To the mixture, was added water (60 mL). The suspension was filtered and washed with water (2×50 mL), ethyl acetate (2×50 mL), sodium hydrogen carbonate (sat, 50 mL) and water (50 mL) to give 3-(2-methyl-4-oxo-8-trifluoromethyl-4H-quinazolin-3-yl)-piperidine-2,6-dione as a white so id (0.32 g, 10% yield): HPLC: Waters Symmetry C18, 5 μm, 3.9×150 mm, 1 mL/min, 240 nm, 35/65 CH3CN/0.1% H3PO4, 7.57 min (99.8%); mp: 351-353° C.; 1H NMR (DMSO-d6) δ 2.19-2.26 (m, 1H, CHH), 2.59-2.70 (m, 5H, CH3, 2CHH), 2.81-2.93 (m, 1H, CHH), 5.34 (dd, J=5, 11 Hz, 1H, NCH), 7.64 (t, J=8 Hz, 1H, Ar), 8.20 (d, J=8 Hz 1H, Ar), 8.31 (d, J=8 Hz, 1H, Ar), 11.09 (s, 1H, NH); 13C NMR (DMSO-d6) δ 20.67, 24.05, 30.57, 56.84, 121.48, 123.52 (q, JC-F=274 Hz), 124.77 (q, JC-F=30 Hz), 125.98, 130.74, 132.29 (q, JC-F=5 Hz), 144.20, 156.71, 159.68, 169.28, 172.58; LCMS: MH=340; Anal Calcd for C15H12N3O3F3+0.3H2O+0.1 CH3CN: C, 52.34; H. 3.72; N, 12.45; F, 16.34. Found: C, 52.71; H, 3.52; N, 12.31; F, 15.99.

Workup

  1. temperatureheated
  2. temperatureto reflux for 22 hours
  3. filtrationThe suspension was filtered
  4. washwashed with water (2×50 mL), ethyl acetate (2×50 mL), sodium hydrogen carbonate (sat, 50 mL) and water (50 mL)

Sources & evidence

ORD record
ord-6d75ffae9c0c45249679f020b28cbd56
Source dataset
uspto-grants-2013_07
Patent number
US08492395B2

Reaction notes

Loading…