Water → HCID 25235919, compound

HRID 453059Notes

Reaction equation

HRID 453059 reaction equation
[NH2:1][C:2]1[C:18]([CH3:19])=[CH:17][CH:16]=[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.CN1C(=O)CCC1>[CH3:19][C:18]1[CH:17]=[CH:16][CH:15]=[C:3]2[C:2]=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

7

Reactant 4

HCID 962Water2×HCID 6101p-Toluenesulfonic acidHCID 9005Trimethyl orthoformateHCID 65955041HCID 65955041, compound

Product 1

HCID 25235919HCID 25235919, compoundYield 72%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

A stirred solution of 2-amino-N-(2,6-dioxo-piperidin-3-yl)-3-methyl-benzamide (0.9 g, 3.4 mmol) and trimethyl orthoformate (4.5 mL) and p-toluene sulfonic acid (250 mg) in acetonitrile (20 mL) was heated to reflux for 17 hours. To the mixture, was added water (75 mL) and stirred for 20 minutes. The suspension was filtered and washed with methanol (20 mL), water (20 mL) and ethyl acetate (20 mL) to give a purple solid. The solid in NMP (4 mL) was heated at 80° C. for 30 minutes. To the solution, was added water (1 mL), and the mixture was allowed to cool to room temperature. The suspension was filtered and washed with water (30 mL) to give 3-(8-methyl-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dione as a light purple solid (660 mg, 72% yield): HPLC: Waters Symmetry C18, 5 μm, 3.9×150 mm, 1 mL/min, 240 nm, 30/70 CH3CN/0.1% H3PO4, 3.07 min (98.6%); mp: 290-292° C.; 1H NMR (DMSO-d6) δ2.11-2.19 (m, 1H, CHH), 2.56 (s, 3H, CH3), 2.62-2.93 (m, 3H, CH2, CHH), 5.48 (br, 1H, NCH), 7.46 (t, J=8 Hz, 1H, Ar), 7.73 (d, J=8 Hz, 1H, Ar), 7.99 (d, J=8 Hz, 1H, Ar), 8.38 (s, 1H, CH), 11.16 (s, 1H, NH); 13C NMR (DMSO-d6) δ 17.01, 22.53, 30.97, 56.22, 121.36, 123.79, 126.51, 126.86, 135.03, 135.47, 136.39, 145.96, 146.36, 159.97, 169.92, 172.52; LCMS: MH=272; Anal Calcd for C14H13N3O3: C, 61.99; H, 4.83; N, 15.49. Found: C, 61.70; H, 4.68; N, 15.40.

Workup

  1. temperatureto reflux for 17 hours
  2. filtrationThe suspension was filtered
  3. washwashed with methanol (20 mL), water (20 mL) and ethyl acetate (20 mL)
  4. customto give a purple solid
  5. filtrationThe suspension was filtered
  6. washwashed with water (30 mL)

Sources & evidence

ORD record
ord-d3b61e8afe134472a75d2ed87d48b2a4
Source dataset
uspto-grants-2013_07
Patent number
US08492395B2

Reaction notes

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