p-Toluenesulfonic acid → HCID 25235687, compound

HRID 509466Notes

Reaction equation

HRID 509466 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].[C:20](OC)(OC)(OC)C.C1(C)C=CC(S(O)(=O)=O)=CC=1>>[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

4

Reactant 3

HCID 6101p-Toluenesulfonic acidHCID 15050Trimethyl orthoacetateHCID 68730412HCID 68730412, compound

Product 1

HCID 25235687HCID 25235687, compoundYield 10%

Procedure

A solution of 2-amino-N-(2,6-dioxo-piperidin-3-yl)-5-bromo-benzamide (1.0 g, 3 mmol) and trimethyl orthoacetate (1.6 mL) and p-toluene sulfonic acid (250 mg) in acetonotrile (10 mL) was heated to reflux for 7 days. The suspension was filtered and washed with ethyl acetate (10 mL), methanol (5 mL) and ethyl acetate (10 mL) to give 3-(6-bromo-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dione as an off-white solid (108 mg, 10% yield): HPLC: Waters Symmetry C18, 5 μm, 3.9×150 mm, 1 mL/min, 240 nm, 30/70 CH3CN/0.1% F3PO4, 5.17 min (98.7%); mp: 273-275° C.; 1H NMR (DMSO-d6) δ 2.14-2.27 (m, 1H, CHH), 2.56-2.69 (m, 2H, 2CHH), 2.64 (s, 3H, CH3), 2.72-2.90 (m, 1H, CHH), 5.29 (dd. J=6, 11 Hz, 1H, NCH), 7.58 (d, J=9 Hz, 1H, Ar), 7.98 (dd, J=2, 9 Hz, 1H, Ar), 8.12 (d, J=2 Hz, 1H, Ar), 11.06 (s, 1H, NH); 13C NMR (DMSO-d6) δ 20.72, 23.42, 30.50, 56.64, 118.80, 121.77, 127.94, 128.95, 137.51, 145.76, 155.74, 159.32, 167.24, 172.49; LCMS: MH=350, 352; Anal Calcd for C14H12N3O3Br: C, 48.02; H, 3.45; N, 12.00. Found: C, 48.02; H, 3.18; N, 11.76.

Workup

  1. temperatureto reflux for 7 days
  2. filtrationThe suspension was filtered
  3. washwashed with ethyl acetate (10 mL), methanol (5 mL) and ethyl acetate (10 mL)

Sources & evidence

ORD record
ord-fed57efc35e04faf8870d9dab1e9d79c
Source dataset
uspto-grants-2015_08
Patent number
US09096573B2

Reaction notes

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