Hydrochloric Acid → HCID 25235774, compound

HRID 453005Notes

Reaction equation

HRID 453005 reaction equation
[NH2:1][C:2]1[CH:10]=[CH:9][C:8]([OH: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.Cl>C(#N)C.CO.O>[OH: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

10

Reactant 6

HCID 313Hydrochloric AcidHCID 795Imidazole2×HCID 6367Acetyl chlorideHCID 7540Triphenyl phosphiteHCID 1345483-Aminopiperidine-2,6-dione hydrochlorideHCID 1645925-Hydroxyanthranilic acid

Product 1

HCID 25235774HCID 25235774, compoundYield 31.3%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

To a stirred mixture of 2-amino-5-hydroxybenzoic acid (5.1 g, 33 mmol) and imidazole (5.0 g, 73 mmol) in acetonitrile (60 mL), was added acetyl chloride (5.2 mL, 73 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 (6.0 g, 37 mmol), imidazole (5.0 g, 73 mmol) and triphenyl phosphite (10.5 mL, 40 mmol) and heated to reflux for 22 hours. To the mixture, was added water (100 mL) and conc HCl until pH ˜1. The solvent was removed in vacuo. To the residue, was added water (50 mL). The aqueous layer was extracted with ethyl acetate (50 mL). To the aqueous layer, was added ethyl acetate (50 mL), and the mixture was stirred at room temperature to give a suspension. The suspension was filtered to give a solid, which was stirred in methanol (50 mL) overnight. The suspension was filtered and washed with methanol (2×30 mL) and water to give 3-(6-hydroxy-2-methyl-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dione as an off-white solid (2.97 g, 31% yield): HPLC: Waters Symmetry C18, 5 μm, 3.9×150 mm, 1 mL/min, 240 nm, 5/95 grad 95/5 in 5 min CH3CN/0.1% H3PO4, 4.50 min (96.8%); mp: 315-317° C.; 1H NMR (DMSO-d6) δ 2.13-2.18 (m, 1H, CH—H), 2.58 (s, 3H, CH3), 2.62-2.71 (m, 2H, 2CH—H), 2.78-2.91 (m, 1H, CH—H), 5.22 (dd, J=6, 11 Hz, 1H, NCH), 7.24-7.32 (m, 2H, Ar), 7.49 (d, J=9 Hz, 1H, Ar), 10.07 (s, 1H, OH), 11.00 (s, 1H, NH); 13C NMR (DMSO-d6) δ 20.97, 23.10, 30.59, 56.36, 108.59, 121.24, 124.13, 128.19, 140.14, 151.39, 155.89, 160.24, 169.58, 172.63; LCMS: MH=288; Anal Calcd for C14H13N3O4+1H2O: C, 55.08; H, 4.95; N, 13.76. Found: C, 54.82; H, 4.74; N, 13.54.

Workup

  1. temperatureheated
  2. temperatureto reflux for 22 hours
  3. customThe solvent was removed in vacuo
  4. additionTo the residue, was added water (50 mL)
  5. extractionThe aqueous layer was extracted with ethyl acetate (50 mL)
  6. additionTo the aqueous layer, was added ethyl acetate (50 mL)
  7. stirringthe mixture was stirred at room temperature
  8. customto give a suspension
  9. filtrationThe suspension was filtered
  10. customto give a solid, which
  11. filtrationThe suspension was filtered
  12. washwashed with methanol (2×30 mL) and water

Sources & evidence

ORD record
ord-524955f3255a4e9d8b2bc542d8d13a71
Source dataset
uspto-grants-2013_07
Patent number
US08492395B2

Reaction notes

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