Imidazole → HCID 25235685, compound

HRID 452998Notes

Reaction equation

HRID 452998 reaction equation
[NH2:1][C:2]1[CH:10]=[CH:9][C:8]([CH3:11])=[CH:7][C:3]=1[C:4]([OH:6])=O.N1[CH:16]=[CH:15]N=C1.C(Cl)(=O)C.Cl.[NH2:22][CH:23]1[CH2:28][CH2:27][C:26](=[O:29])[NH:25][C:24]1=[O:30].P(OC1C=CC=CC=1)(OC1C=CC=CC=1)OC1C=CC=CC=1>C(#N)C.CN(C=O)C.O>[CH3:15][C:16]1[N:22]([CH:23]2[CH2:28][CH2:27][C:26](=[O:29])[NH:25][C:24]2=[O:30])[C:4](=[O:6])[C:3]2[C:2](=[CH:10][CH:9]=[C:8]([CH3:11])[CH:7]=2)[N:1]=1

Participants

9

Reactant 5

HCID 795Imidazole2×HCID 6367Acetyl chlorideHCID 7540Triphenyl phosphiteHCID 762552-Amino-5-methylbenzoic acidHCID 1345483-Aminopiperidine-2,6-dione hydrochloride

Product 1

HCID 25235685HCID 25235685, compoundYield 38%

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolvent

Procedure

To a stirred mixture of 2-amino-5-methylbenzoic acid (4.8 g, 32 mmol) and imidazole (2.6 g, 38 mmol) in acetonitrile (100 mL), was added acetyl chloride (2.7 mL, 38 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 (5.2 g, 32 mmol), imidazole (4.7 g, 70 mmol) and triphenyl phosphite (9.9 mL, 38 mmol) and heated to reflux for 22 hours. To the mixture, was added water (100 mL). The suspension was filtered and washed with water (2×100 mL), ethyl acetate (2×100 mL), sodium hydrogen carbonate (sat, 100 mL) and water (100 mL) to give a white solid, which was stirred in DMF (40 mL) overnight. The suspension was filtered and washed with DMF (5 mL) to give a white solid. The solid was stirred in water (100 mL) at 60° C. for 2 hours, then at room temperature overnight. The suspension was filtered and washed with water (2×50 mL) to give 3-(2,6-dimethyl-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dione as a white solid (3.4 g, 38% yield): HPLC: Waters Symmetry C18, 5 μm, 3.9×150 mm, 1 mL/min, 240 nm, 20/80 CH3CN/0.1% H3PO4, 5.37 min (99.8%); mp: 270-272° C.; 1H NMR (DMSO-d6) δ 2.10-2.22 (m, 1H, CHH), 2.43 (s, 3H, CH3), 2.56-2.72 (m, 5H, CH3, 2CHH), 2.76-2.92 (m, 1H, CHH), 5.24 (dd, J=6, 11 Hz, 1H, NCH), 7.52 (d, J=8 Hz, 1H, Ar), 7.64 (dd, J=2, 8 Hz, 1H, Ar), 7.82 (s, 1H, Ar), 11.02 (s, 1H, NH); 13C NMR (DMSO-d6) δ 20.76, 20.95, 23.34, 30.60, 56.47, 120.05, 125.20, 126.39, 135.96, 136.19, 144.87, 153.99, 160.40, 169.53, 172.62; LCMS: MH=286; Anal Calcd for C15H15N3O3+2H2O: C, 56.07; H, 5.96; N, 13.08. Found: C, 55.73; H, 5.75; N, 13.01.

Workup

  1. temperatureheated
  2. temperatureto reflux for 22 hours
  3. filtrationThe suspension was filtered
  4. washwashed with water (2×100 mL), ethyl acetate (2×100 mL), sodium hydrogen carbonate (sat, 100 mL) and water (100 mL)
  5. customto give a white solid, which
  6. filtrationThe suspension was filtered
  7. washwashed with DMF (5 mL)
  8. customto give a white solid
  9. customat room temperature
  10. customovernight
  11. filtrationThe suspension was filtered
  12. washwashed with water (2×50 mL)

Sources & evidence

ORD record
ord-12f4bb794af543fd8d02ffb807c754e8
Source dataset
uspto-grants-2013_07
Patent number
US08492395B2

Reaction notes

Loading…