3-(Trifluoromethyl)benzoic acid → HCID 24964384, compound

HRID 1409660Notes

Reaction equation

HRID 1409660 reaction equation
[F:1][C:2]([F:13])([F:12])[C:3]1[CH:4]=[C:5]([CH:9]=[CH:10][CH:11]=1)[C:6]([OH:8])=O.C(N1C=CN=C1)(N1C=CN=C1)=O.Cl.[NH2:27][CH2:28][C:29]1[CH:38]=[CH:37][CH:36]=[C:35]2[C:30]=1[C:31](=[O:48])[N:32]([CH:40]1[CH2:45][CH2:44][C:43](=[O:46])[NH:42][C:41]1=[O:47])[C:33]([CH3:39])=[N:34]2>CN(C=O)C>[O:47]=[C:41]1[CH:40]([N:32]2[C:31](=[O:48])[C:30]3[C:35](=[CH:36][CH:37]=[CH:38][C:29]=3[CH2:28][NH:27][C:6](=[O:8])[C:5]3[CH:9]=[CH:10][CH:11]=[C:3]([C:2]([F:1])([F:13])[F:12])[CH:4]=3)[N:34]=[C:33]2[CH3:39])[CH2:45][CH2:44][C:43](=[O:46])[NH:42]1

Participants

5

Reactant 3

HCID 99633-(Trifluoromethyl)benzoic acidHCID 682631,1'-CarbonyldiimidazoleHCID 249683051015474-47-1

Product 1

HCID 24964384HCID 24964384, compoundYield 62.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of 3-trifluoromethyl-benzoic acid (0.28 g, 1.5 mmol) in DMF (8 mL) in a 40° C. oil bath, was added 1,1′carbonyldiimidazole (0.27 g, 1.6 mmol) and stirred for one hour. Then 3-(5-aminomethyl-2-methyl-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dione hydrogen chloride (0.50 g, 1.5 mmol) was added and stirred for 15 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-trifluoromethyl-benzamide as an off-white solid (440 mg, 62% 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, 6.37 min (98.3%); mp, 233-235° C.; 1HNMR (DMSO-d6) 2.17-2.23 (m, 1H, CHH), 2.58-2.91 (m, 6H, CHCH2, CH3), 4.95-5.12 (m, 2H, CH2NH), 5.27 (dd, J=6, 11 Hz, 1H, CH), 7.36-8.27 (m, 7H, Ar), 9.23 (t, J=5 Hz, 1H, CH2NH), 11.05 (s, 1H, NH); 13C NMR (DMSO-d6) δ 20.79, 23.29, 30.60, 42.29, 56.52, 117.68, 123.85 (q, JC-F=3 Hz), 123.98 (d, JC-F3=273 Hz), 124.15, 125.53, 127.90 (d, JC-F=3 Hz), 129.19 (d, JC-F=32 Hz), 129.72, 131.37, 133.97, 135.05, 140.50, 148.50, 154.86, 161.07, 164.85, 169.54, 172.62. LCMS MH=473; Anal Calcd For C23H19N4O4F3: C, 58.48; H, 4.05; N, 11.86; F, 12.06. Found: C, 58.19; H, 3.84; N, 11.86; F, 12.00.

Workup

  1. stirringstirred for 15 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-eaa2d86058854addb15ef8e9209833e5
Source dataset
uspto-grants-2014_12
Patent number
US08921385B2

Reaction notes

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