3-Methylbenzoic acid → HCID 24963673, compound

HRID 1409653Notes

Reaction equation

HRID 1409653 reaction equation
[C:1]1([CH3:10])[CH:6]=[CH:5][CH:4]=[C:3]([C:7]([OH:9])=O)[CH:2]=1.C(N1C=CN=C1)(N1C=CN=C1)=O.Cl.[NH2:24][CH2:25][C:26]1[CH:35]=[CH:34][CH:33]=[C:32]2[C:27]=1[C:28](=[O:45])[N:29]([CH:37]1[CH2:42][CH2:41][C:40](=[O:43])[NH:39][C:38]1=[O:44])[C:30]([CH3:36])=[N:31]2>CN(C=O)C>[O:44]=[C:38]1[CH:37]([N:29]2[C:28](=[O:45])[C:27]3[C:32](=[CH:33][CH:34]=[CH:35][C:26]=3[CH2:25][NH:24][C:7](=[O:9])[C:3]3[CH:4]=[CH:5][CH:6]=[C:1]([CH3:10])[CH:2]=3)[N:31]=[C:30]2[CH3:36])[CH2:42][CH2:41][C:40](=[O:43])[NH:39]1

Participants

5

Reactant 3

HCID 74183-Methylbenzoic acidHCID 682631,1'-CarbonyldiimidazoleHCID 249683051015474-47-1

Product 1

HCID 24963673HCID 24963673, compoundYield 76%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of m-toluic acid (0.24 g, 1.8 mmol) in DMF (8 mL) in a 40° C. oil bath, was added 1,1′carbonyldiimidazole (0.31 g, 1.9 mmol) and stirred for one hour. To the mixture, 3-(5-aminomethyl-2-methyl-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dione hydrogen chloride (0.59 g, 1.8 mmol) was added, and the mixture was stirred for 45 minutes. The solvent was evaporated, and the residue was purified by flash column chromatography (Silica gel, methanol/methylene chloride 4%/96%) to give N-[3-(2,6-dioxo-piperidin-3-yl)-2-methyl-4-oxo-3,4-dihydro-quinazolin-5-ylmethyl]-3-methyl-benzamide as a light green solid (560 mg, 76% yield); HPLC, Waters Symmetry C18, 5 μm, 3.9×150 mm, 1 mL/min, 240 nm, 10/90 CH3CN/0.1% H3PO4, grad. to 95/5 in 5 min, kept 5 min, 6.00 min (99.2%); mp, 263-265° C.; 1HNMR (DMSO-d6)2.18-2.21 (m, 1H, CHH), 2.38 (s, 3H, CH3Ar), 2.59-2.88 (m, 6H, CHCH2, CH3), 4.95-5.12 (m, 2H, CH2NH), 5.26 (dd, J=6, 11 Hz, 1H, CH), 7.33-7.76 (m, 7H, Ar), 8.89 (t, J=5 Hz, 1H, CH2NH), 11.05 (s, 1H, NH); 13C NMR (DMSO-d6) δ 20.83, 20.92, 23.29, 30.60, 42.12, 56.52, 117.65, 123.98, 124.32, 125.40, 127.76, 128.26, 131.85, 133.93, 134.23, 137.65, 141.04, 148.50, 154.80, 161.11, 166.39, 169.53, 172.61. LCMS MH=419; Anal Calcd For C23H22N4O4+0.6H2O: C, 64.36; H, 5.45; N, 13.05. Found: C, 64.36; H, 5.24; N, 13.22.

Workup

  1. stirringthe mixture was stirred for 45 minutes
  2. customThe solvent was evaporated
  3. customthe residue was purified by flash column chromatography (Silica gel, methanol/methylene chloride 4%/96%)

Sources & evidence

ORD record
ord-a1bc7b413cd241be8c7e46033c8da299
Source dataset
uspto-grants-2014_12
Patent number
US08921385B2

Reaction notes

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