Imidazole → HCID 25235688, compound

HRID 509463Notes

Reaction equation

HRID 509463 reaction equation
[NH2:1][C:2]1[CH:10]=[CH:9][C:8]([F: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>[F:11][C:8]1[CH:7]=[C:3]2[C:2](=[CH:10][CH:9]=1)[N:1]=[C:15]([CH3:16])[N:22]([CH:23]1[CH2:28][CH2:27][C:26](=[O:29])[NH:25][C:24]1=[O:30])[C:4]2=[O:6]

Participants

7

Reactant 5

HCID 795Imidazole2×HCID 6367Acetyl chlorideHCID 7540Triphenyl phosphiteHCID 1014122-Amino-5-fluorobenzoic acidHCID 1345483-Aminopiperidine-2,6-dione hydrochloride

Product 1

HCID 25235688HCID 25235688, compoundYield 53.9%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a stirred mixture of 2-amino-5-fluorobenzoic acid (1.2 g, 7.8 mmol) and imidazole (0.63 g, 9.3 mmol) in acetonitrile (15 mL), was added acetyl chloride (0.66 mL, 9.3 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 (1.3 g, 7.7 mmol), imidazole (1.2 g, 17 mmol) and triphenyl phosphite (2.2 mL, 8.5 mmol) and heated to reflux for 22 hours. The suspension was filtered and washed with water (2×50 mL), ethyl acetate (2×50 mL), and water (50 mL) to give 3-(6-fluoro-2-methyl-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dione as a white solid (1.2 g, 53% yield): HPLC: Waters Symmetry C18, 5 μm, 3.9×150 mm, 1 mL/min. 240 nm, 20/80 CH3CN/0.1% H3PO4, 5.99 min (99.3%); mp: 273-275° C.; 1H NMR (DMSO-d6) δ 2.13-2.23 (m, 1H, CHH), 2.57-2.71 (m, 5H, CH3, 2CHH), 2.75-2.95 (m, 1H, CHH), 5.30 (dd, J=6, 11 Hz, 1H, NCH), 7.70-7.73 (m, 3H, Ar), 11.06 (s, 1H. NH); 13C NMR (DMSO-d6) δ 20.82, 23.31, 30.58, 56.63, 110.54 (d, JC-F=23 Hz), 121.40 (d, JC-F=8 Hz), 123.24 (d, JC-F=24 Hz), 129.47 (d, JC-F=8 Hz), 143.75, 154.45, 159.83 (d. JC-F=245 Hz), 159.86 (d, JC-F=3 Hz), 169.37, 172.58; LCMS: MH=290; Anal Calcd for C14H12N3O3F 1.3H2O: C, 53.78; H, 4.71; N, 13.44. Found: C, 53.75; H, 4.61; N, 13.50.

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), and water (50 mL)

Sources & evidence

ORD record
ord-18806b83a7754d0fbf9bd2cd19f7969c
Source dataset
uspto-grants-2015_08
Patent number
US09096573B2

Reaction notes

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