Imidazole → HCID 25235872, compound

HRID 453037Notes

Reaction equation

HRID 453037 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, CH—H), 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-cc8940d0ca80441a89d2835b9eb306d6
Source dataset
uspto-grants-2013_07
Patent number
US08492395B2

Reaction notes

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