p-Toluenesulfonic acid → HCID 25235914, compound

HRID 453041Notes

Reaction equation

HRID 453041 reaction equation
[NH2:1][C:2]1[CH:18]=[C:17]([F:19])[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>CO>[F:19][C:17]1[CH:18]=[C:2]2[C:3]([C:4](=[O:5])[N:6]([CH:7]3[CH2:12][CH2:11][C:10](=[O:13])[NH:9][C:8]3=[O:14])[CH:20]=[N:1]2)=[CH:15][CH:16]=1

Participants

5

Reactant 3

HCID 6101p-Toluenesulfonic acidHCID 9005Trimethyl orthoformateHCID 65969733HCID 65969733, compound

Product 1

HCID 25235914HCID 25235914, compoundYield 70%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of 2-amino-N-(2,6-dioxo-piperidin-3-yl)-4-fluoro-benzamide (0.9 g, 3.4 mmol) and trimethyl orthoformate (4 mL) and p-toluene sulfonic acid (110 mg) was heated to 160° C. in a microwave oven for 15 minutes. To the mixture, was added methanol (10 mL), and the mixture was stirred for 10 minutes. The suspension was filtered and washed with methanol to give 3-(7-fluoro-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dione as a white solid (650 mg, 70% yield): HPLC: Waters Symmetry C18, 5 μm, 3.9×150 mm, 1 mL/min, 240 nm, 30/70 CH3CN/0.1% H3PO4, 2.45 min (96.1%); mp: 296-298° C.; 1H NMR (DMSO-d6) δ 2.13-2.19 (m, 1H, CHH), 2.63-2.73 (m, 2H, 2CHH), 2.82-2.93 (m, 1H, CHH), 5.50 (br, 1H, NCH), 7.46 (dt, J=3, 9 Hz, 1H, Ar), 7.53 (dd, J=3, 10 Hz, 1H, Ar), 8.22 (dd, J=6, 9 Hz, 1H, Ar), 8.42 (s, 1H, CH), 11.18 (s, 1H, NH); 13C NMR (DMSO-d6) δ 22.45, 30.88, 56.43, 112.3 (d, JC-F=22 Hz), 115.91 (d, JC-F=23 Hz), 118.38, 129.32 (d, JC-F=11 Hz), 148.71, 149.65 (d, JC-F=14 Hz), 159.00, 165.70 (d, JC-F=252 Hz), 169.76, 172.41; LCMS: MH=276; Anal Calcd for C13H10N3O3F: C, 56.73; H, 3.66; N, 15.27. Found: C. 56.39; H, 3.60; N, 15.16.

Workup

  1. filtrationThe suspension was filtered
  2. washwashed with methanol

Sources & evidence

ORD record
ord-9c93285de79d4d7f8189ac78d860dd55
Source dataset
uspto-grants-2013_07
Patent number
US08492395B2

Reaction notes

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