Water → HCID 25235687, compound

HRID 509470Notes

Reaction equation

HRID 509470 reaction equation
[NH2:1][C:2]1[CH:18]=[CH:17][C:16]([Br:19])=[CH:15][C:3]=1[C:4]([NH:6][CH:7]1[CH2:12][CH2:11][C:10](=[O:13])[NH:9][C:8]1=[O:14])=[O:5].[CH:20](OC)(OC)OC.C1(C)C=CC(S(O)(=O)=O)=CC=1.O>C(#N)C>[Br:19][C:16]1[CH:15]=[C:3]2[C:2](=[CH:18][CH:17]=1)[N:1]=[CH:20][N:6]([CH:7]1[CH2:12][CH2:11][C:10](=[O:13])[NH:9][C:8]1=[O:14])[C:4]2=[O:5]

Participants

6

Reactant 4

HCID 962WaterHCID 6101p-Toluenesulfonic acidHCID 9005Trimethyl orthoformateHCID 68730412HCID 68730412, compound

Product 1

HCID 25235687HCID 25235687, compoundYield 68%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A solution of 2-amino-N-(2,6-dioxo-piperidin-3-yl)-5-bromo-benzamide (0.51 g, 1.5 mmol) and trimethyl orthoformate (2 mL) and p-toluene sulfonic acid (150 mg) in acetonitrile (10 mL) was heated to reflux for 12 hours. To the mixture, was added water (70 mL), and stirred at room temperature for 2 hours. The suspension was filtered and washed with ethyl acetate (10 mL). The solid in NMP (3 mL) was heated at 80° C. To the solution, was added water (1.5 mL), and the mixture was allowed to cool to room temperature. The suspension was filtered and washed with NMP (1 mL) and ethyl acetate (10 mL) to give 3-(6-bromo-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dione as a white solid (350 mg, 68% yield): HPLC: Waters Symmetry C18, 5 μm, 3.9×150 mm, 1 mL/min, 240 nm, 30/70 CH3CN/0.1% H2PO4, 4.18 min (99.9%); mp: 312-314° C.; 1H NMR (DMSO-d6) δ 2.14-2.21 (m, 1H, CHH), 2.60-2.74 (m, 2H, 2CHH), 2.83-2.93 (m, 1H, CHH), 5.51 (brs, 1H, NCH), 7.68 (d, J=9 Hz, 1H, Ar), 8.03 (dd, J=2, 9 Hz, 1H, Ar), 8.24 (d, J=2 Hz, 1H, Ar), 8.42 (5, 1H, CH), 11.19 (s, 1H, NH); NMR (DMSO-d6) δ 22.45, 30.93, 55.49, 119.83, 122.96, 128.23, 129.65, 137.61, 146.52, 147.94, 158.66, 169.75, 172.46; LCMS: MH=336, 338; Anal Calcd for C13H10N3O1Br+0.3H2O: C, 45.72; H, 3.13; N, 12.30; Br, 23.39. Found: C, 45.46; H, 2.75; N, 12.15; Br, 22.81.

Workup

  1. temperatureto reflux for 12 hours
  2. filtrationThe suspension was filtered
  3. washwashed with ethyl acetate (10 mL)
  4. temperatureThe solid in NMP (3 mL) was heated at 80° C
  5. additionTo the solution, was added water (1.5 mL)
  6. temperatureto cool to room temperature
  7. filtrationThe suspension was filtered
  8. washwashed with NMP (1 mL) and ethyl acetate (10 mL)

Sources & evidence

ORD record
ord-7701ccdc54b04fadba7a290634d6c7ec
Source dataset
uspto-grants-2015_08
Patent number
US09096573B2

Reaction notes

Loading…