Imidazole → HCID 25235872, compound

HRID 509498Notes

Reaction equation

HRID 509498 reaction equation
[NH2:1][C:2]1[CH:10]=[C:9]([Cl:11])[CH:8]=[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>[Cl:11][C:9]1[CH:10]=[C:2]2[C:3]([C:4](=[O:6])[N:22]([CH:23]3[CH2:28][CH2:27][C:26](=[O:29])[NH:25][C:24]3=[O:30])[C:15]([CH3:16])=[N:1]2)=[CH:7][CH:8]=1

Participants

7

Reactant 5

HCID 795Imidazole2×HCID 6367Acetyl chlorideHCID 7540Triphenyl phosphiteHCID 666462-Amino-4-chlorobenzoic acidHCID 1345483-Aminopiperidine-2,6-dione hydrochloride

Product 1

HCID 25235872HCID 25235872, compoundYield 73.3%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a stirred mixture of 2-amino-4-chlorobenzoic acid (5.0 g, 29 mmol) and imidazole (2.4 g, 35 mmol) in acetonitrile (50 mL), was added acetyl chloride (2.5 mL, 35 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 (4.8 g, 29 mmol), imidazole (4.4 g, 64 mmol) and triphenyl phosphite (8.4 mL, 32 mmol) and heated to reflux for 22 hours. The suspension was filtered and washed with acetonitrile (50 mL) and water (2×50 mL) to give 3-(7-chloro-2-methyl-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dione as a white solid (6.5 g, 73% yield): HPLC: Waters Symmetry C18, 5 μm, 3.9×150 mm, 1 mL/min, 240 nm, 30/70 CH3CN/0.1% H3PO4, 4.36 min (99.9%); mp: 291-293° C.; 1H NMR (DMSO-d6) δ 2.16-2.23 (m, 1H, CHH), 2.59-2.72 (m, 5H, CH3, 2CHH), 2.79-2.92 (m, 1H, CHH), 5.29 (dd, J=5, 11 Hz, 1H, NCH), 7.53 (dd, J=2.9 Hz, 1H, Ar), 7.69 (d, J=8 Hz, 1H, Ar), 8.03 (d, J=8 Hz, 1H. Ar), 11.07 (s, 1H, NH); 13C NMR (DMSO-d6) δ 20.84, 23.53, 30.58, 56.65, 19.06, 125.70, 126.91, 128.07, 139.30, 147.89, 156.74, 159.89, 169.35, 172.58; LCMS: MH=306, 308; Anal Calcd for C14H12N3O3Cl: C, 55.00; H, 3.96; N, 13.74; Cl, 11.60. Found: C, 55.24; H, 3.78; N, 13.74; Cl, 12.01.

Workup

  1. temperatureheated
  2. temperatureto reflux for 22 hours
  3. filtrationThe suspension was filtered
  4. washwashed with acetonitrile (50 mL) and water (2×50 mL)

Sources & evidence

ORD record
ord-a07724d14d3c411992c88d2e61e4dc4a
Source dataset
uspto-grants-2015_08
Patent number
US09096573B2

Reaction notes

Loading…