Benzoyl chloride, 3,4-dichloro- → HCID 24964383, compound

HRID 509494Notes

Reaction equation

HRID 509494 reaction equation
Cl.NC[C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][CH:13]=1)[N:10]=[C:9]([CH3:14])[N:8]([CH:15]1[CH2:20][CH2:19][C:18](=[O:21])[NH:17][C:16]1=[O:22])[C:7]2=[O:23].[Cl:24][C:25]1[CH:26]=[C:27]([CH:31]=[CH:32][C:33]=1[Cl:34])[C:28](Cl)=[O:29].[CH:35]([N:38](CC)C(C)C)(C)C>C(#N)C>[Cl:24][C:25]1[CH:26]=[C:27]([CH:31]=[CH:32][C:33]=1[Cl:34])[C:28]([NH:38][CH2:35][C:5]1[CH:4]=[CH:13][CH:12]=[C:11]2[C:6]=1[C:7](=[O:23])[N:8]([CH:15]1[CH2:20][CH2:19][C:18](=[O:21])[NH:17][C:16]1=[O:22])[C:9]([CH3:14])=[N:10]2)=[O:29]

Participants

5

Reactant 3

HCID 76403Benzoyl chloride, 3,4-dichloro-HCID 81531DiisopropylethylamineHCID 687303673-(6-(aminomethyl)-2-methyl-4-oxoquinazolin-3(4H)-yl)piperidine-2,6-dione hydrochloride

Product 1

HCID 24964383HCID 24964383, compoundYield 46%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a stirred suspension of 3-(6-aminomethyl-2-methyl-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dione hydrogen chloride (0.45 g, 1.4 mmol) in acetonitrile (10 mL), was added 3,4-dichloro-benzoyl chloride (0.34 g, 1.6 mmol) and N,N-diisopropyl ethylamine (0.54 mL, 3.2 mmol). The mixture was stirred at room temperature 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 3,4-dichloro-N-[3-(2,6-dioxo-piperidin-3-yl)-2-methyl-4-oxo-3,4-dihydro-quinazolin-5-ylmethyl]-benzamide as an off-white solid (290 mg, 46% yield); HPLC, Waters Symmetry C18, 5 nm, 3.9×150 mm, 1 mL/min, 240 nm, 10/90 CH3CN/0.1% F3PO4, gradient to 95/5 in 5 min, kept for 5 min, 6.45 min (99.6%); mp, 177-179° C.; 1HNMR (DMSO-d6) δ 2.16-2.18 (m, 1H, CHH), 2.56-2.84 (m, 6H, CHCH2, CH), 4.59 (d, J=5 Hz, 2H, CH2NH), 5.26 (dd, J=5, 9 Hz, 1H, CH), 7.58-8.14 (m, 6H, Ar), 9.34 (t, J=5 Hz, 1H, CH2NH), 11.02 (s, 1H, NH); 13C NMR (DMSO-d6) δ 20.91, 23.41, 30.61, 42.47, 56.54, 120.01, 124.04, 126.66, 127.56, 129.20, 130.77, 131.32, 134.17, 134.37, 137.71, 145.88, 154.65, 160.42, 164.00, 169.45, 172.60. LCMS MH=473, 475; Anal Calcd For C22H18N4O4Cl2+1.0 CH2Cl2: C, 53.78; H, 4.10; N, 11.40; Cl, 14.43. Found: C, 53.44; H, 4.11; N, 11.27; Cl, 14.80.

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-07586d72355a44599571367fbaa41d63
Source dataset
uspto-grants-2015_08
Patent number
US09096573B2

Reaction notes

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