Triethylamine → HCID 24968306, compound

HRID 1868275Notes

Reaction equation

HRID 1868275 reaction equation
Cl.[NH2:2][CH2:3][C:4]1[CH:13]=[CH:12][CH:11]=[C:10]2[C:5]=1[C:6](=[O:23])[N:7]([CH:15]1[CH2:20][CH2:19][C:18](=[O:21])[NH:17][C:16]1=[O:22])[C:8]([CH3:14])=[N:9]2.C1(C)C=CC(C(Cl)=O)=CC=1.C(N(CC)CC)C>O1CCCC1>[NH2:2][CH2:3][C:4]1[CH:13]=[CH:12][CH:11]=[C:10]2[C:5]=1[C:6](=[O:23])[N:7]([CH:15]1[CH2:20][CH2:19][C:18](=[O:21])[NH:17][C:16]1=[O:22])[C:8]([CH3:14])=[N:9]2

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 134054-Methylbenzoyl ChlorideHCID 249683051015474-47-1

Product 1

HCID 24968306HCID 24968306, compoundYield 85.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred mixture of 3-(5-aminomethyl-2-methyl-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dione hydrogen chloride (0.47 g, 1.4 mmol) in tetrahydrofuran (10 mL), was added p-toluoyl chloride (0.37 mL, 2.8 mmol) and triethylamine (0.79 mL, 5.6 mmol). The mixture was stirred at room temp overnight. The solvent was evaporated, and the residue was purified by flash column chromatography (Silica gel, methanol/methylene chloride 4%/96%) to give 3-(5-aminomethyl-2-methyl-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dione as a white solid (360 mg, 61% yield); HPLC, Waters Symmetry C18, 5 μm, 3.9×150 mm, 1 mL/min, 240 nm, 10/90 CH3CN/0.1% H3PO4, gradient to 95/5 in 5 min, kept for 5 min, 5.97 min (97.3%); mp, 283-285° C.; 1HNMR (DMSO-d6) 2.17-2.23 (m, 1H, CHH), 2.37 (s, 3H, CH3), 2.58-2.92 (m, 6H, CHCH2, CH3), 4.90-5.07 (m, 2H, CH2NH), 5.25 (dd, J=6, 11 Hz, 1H, Ch, 7.29-7.84 (m, 7H, Ar), 8.85 (t, 1H, J=6 Hz, CH2NH), 11.05 (s, 1H, NH); 13C NMR (DMSO-d6) δ 20.82, 20.93, 23.29, 30.60, 42.07, 56.53, 117.65, 120.97, 124.02, 125.40, 127.21, 128.89, 131.43, 133.92, 141.11, 141.17, 148.50, 154.80, 161.11, 166.14, 169.54, 172.62. LCMS MH=419; Anal Calcd For C23H22N4O4+0.4H2O: C, 64.90; H, 5.40; N, 13.16. Found: C, 64.96; H, 5.37; N, 13.15.

Workup

  1. customThe solvent was evaporated
  2. customthe residue was purified by flash column chromatography (Silica gel, methanol/methylene chloride 4%/96%)

Sources & evidence

ORD record
ord-edc8f5ef93994f73b7cf18484b033d75
Source dataset
uspto-grants-2009_12
Patent number
US07635700B2

Reaction notes

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