4-(Trifluoromethyl)benzoyl chloride → HCID 24964025, compound

HRID 1409656Notes

Reaction equation

HRID 1409656 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.[F:24][C:25]([F:36])([F:35])[C:26]1[CH:34]=[CH:33][C:29]([C:30](Cl)=[O:31])=[CH:28][CH:27]=1.C(N(CC)C(C)C)(C)C>C(#N)C>[O:22]=[C:16]1[CH:15]([N:7]2[C:6](=[O:23])[C:5]3[C:10](=[CH:11][CH:12]=[CH:13][C:4]=3[CH2:3][NH:2][C:30](=[O:31])[C:29]3[CH:33]=[CH:34][C:26]([C:25]([F:24])([F:35])[F:36])=[CH:27][CH:28]=3)[N:9]=[C:8]2[CH3:14])[CH2:20][CH2:19][C:18](=[O:21])[NH:17]1

Participants

5

Reactant 3

HCID 676074-(Trifluoromethyl)benzoyl chlorideHCID 81531DiisopropylethylamineHCID 249683051015474-47-1

Product 1

HCID 24964025HCID 24964025, compoundYield 68.4%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a stirred mixture of 3-(5-aminomethyl-2-methyl-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dione hydrogen chloride (0.45 g, 1.3 mmol) in acetonitrile (10 mL), was added 4-trifluoromethyl-benzoyl chloride (0.30 mL, 2.0 mmol) and N,N-diisopropyl ethylamine (0.58 mL, 3.3 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 N-[3-(2,6-dioxo-piperidin-3-yl)-2-methyl-4-oxo-3,4-dihydro-quinazolin-5-ylmethyl]-4-trifluoromethyl-benzamide as a white solid (420 mg, 67% 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, 6.46 min (97.2%); mp, 253-255° C.; 1HNMR (DMSO-d6)2.18-2.24 (m, 1H, CHH), 2.59-2.94 (m, 6H, CHCH2, CH3), 4.94-5.11 (m, 2H, CH2NH), 5.27 (dd, J=6, 11 Hz, 1H, CH), 7.36-8.13 (m, 7H, Ar), 9.16 (t, J=5 Hz, 1H, CH2NH), 11.06 (s, 1H, NH); 13C NMR (DMSO-d6) δ 20.82, 23.28, 30.60, 42.31, 56.56, 117.68, 124.28, 125.39, 125.44, 125.57, 125.74, 128.16, 130.99, 131.41, 133.98, 137.96, 140.45, 148.50, 154.89, 161.10, 165.12, 169.54, 172.63. LCMS MH=473; Anal Calcd For C23H19N4O4F3+0.5H2O: C, 57.38; H, 4.19; N, 11.64; F, 11.84. Found: C, 57.01; H, 4.05; N, 11.53; F, 11.56.

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-c18cc93a973c4107b32add13c1ec40cf
Source dataset
uspto-grants-2014_12
Patent number
US08921385B2

Reaction notes

Loading…