Imidazole → HCID 24967593, compound

HRID 1868228Notes

Reaction equation

HRID 1868228 reaction equation
[NH2:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]([C:11]([F:14])([F:13])[F:12])[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](=[CH:10][CH:9]=[CH:8][C:7]=2[C:11]([F:14])([F:13])[F:12])[N:1]=1

Participants

8

Reactant 5

HCID 795Imidazole2×HCID 6367Acetyl chlorideHCID 7540Triphenyl phosphiteHCID 1345483-Aminopiperidine-2,6-dione hydrochlorideHCID 27785082-Amino-6-(trifluoromethyl)benzoic acid

Product 1

HCID 24967593HCID 24967593, compoundYield 51%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

To a stirred mixture of 2-amino-6-(trifluoromethyl)benzoic acid (3.0 g, 15 mmol) and imidazole (1.2 g, 18 mmol) in acetonitrile (30 mL), was added acetyl chloride (1.3 mL, 18 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 (2.4 g, 15 mmol), imidazole (2.2 g, 32 mmol) and triphenyl phosphite (4.6 mL, 18 mmol) and heated to reflux for 22 hours. To the mixture, was added water (100 mL). The suspension was filtered and washed with water (2×50 mL), ethyl acetate (2×50 mL), sodium hydrogen carbonate (sat, 50 mL) and water (50 mL) to give 3-(2-methyl-4-oxo-5-trifluoromethyl-4H-quinazolin-3-yl)-piperidine-2,6-dione as a white solid (2.02 g, 51% yield): HPLC: Waters Symmetry Cl8, 5 μm, 3.9×150 mm, 1 mL/min, 240 nm, 30/70 CH3CN/0.1% H3PO4, 4.84 min (99.9%); mp: 268-270° C.; 1H NMR (DMSO-d6) δ 2.14-2.22 (m, 1H, CHH), 2.55-2.70 (m, 5H, CH3, 2CHH, 2.76-2.92 (m, 1H, CHH), 5.29 (dd, J=6, 11 Hz, 1H, NCH), 7.89-7.98 (m, 3H, Ar), 11.06 (s, 1H, NH); 13C NMR (DMSO-d6) δ 20.45, 23.27, 30.43, 56.74, 117.19, 123.19 (q, JC-F=273 Hz), 125.75 (q, JC-F=7 Hz), 126.42 (q, JC-F=32 Hz), 132.05, 133.97, 149.12, 156.58, 157.59, 169.19, 172.48; LCMS: MH=340; Anal Calcd for C15H12N3O3F3+1H2O: C, 50.43; H, 3.95; N, 11.76; F, 15.95. Found: C, 50.26; H, 3.82; N, 11.66; F, 15.71.

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-3d34436bb0274cc4b396a29d898d7ff2
Source dataset
uspto-grants-2009_12
Patent number
US07635700B2

Reaction notes

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