p-Toluenesulfonic acid → HCID 25235729, compound

HRID 509469Notes

Reaction equation

[NH2:1][C:2]1[CH:18]=[CH:17][C:16]([Cl: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>>[Cl: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

Reactant 3

HCID 6101p-Toluenesulfonic acid

HCID 9005Trimethyl orthoformate

HCID 65954232HCID 65954232, compound

Product 1

HCID 25235729HCID 25235729, compoundYield 74%

Procedure

A solution of 2-amino-N-(2,6-dioxo-piperidin-3-yl)-5-chloro-benzamide (0.31 g, 1.1 mmol) and trimethyl orthoformate (4 mL) and p-toluene sulfonic acid (50 mg) was heated to 150° C. in a microwave oven for 10 minutes. The suspension was filtered and washed with ethyl acetate (10 mL), methanol (5 mL) and ethyl acetate (10 mL) to give 3-(6-chloro-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dione as a white solid (230 mg, 74% yield): HPLC: Waters Symmetry C18, 5 μm, 3.9×150 mm, 1 mL/min, 240 nm, 30/70 CH3CN/0.1% H3PO4, 4.01 min (100%); mp: 302-305° C.; 1H NMR (DMSO-d6) δ 2.13-2.20 (m, 1H, CHH), 2.62-2.93 (m, 3H, CH2, CHH), 5.52 (br, 1H, NCH), 7.76 (d, J=9 Hz, 1H, Ar), 7.91 (dd, J=2, 9 Hz, 1H, Ar), 8.10 (d, J=2 Hz, 1H, Ar), 8.41 (s, 1H, CH), 11.19 (s, 1H, NH); 13C NMR (DMSO-d6) δ 22.39, 30.87, 56.29 (br), 122.56, 125.05, 129.47, 131.59, 134.82, 146.19, 147.75, 158.73, 169.68, 172.39; LCMS: MH=292, 294; Anal Calcd for C13H10N3O3Cl: C, 53.53; H, 3.46; N, 14.41. Found: C, 53.43; H, 3.21; N, 14.27.

Workup

filtrationThe suspension was filtered
washwashed with ethyl acetate (10 mL), methanol (5 mL) and ethyl acetate (10 mL)

Sources & evidence

ORD record: ord-7c58a697541c4a96ad3b489ef044c35e
Source dataset: uspto-grants-2015_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09096573B2

Reaction notes

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