Diisopropylethylamine → HCID 25235825, compound

HRID 453032Notes

Reaction equation

HRID 453032 reaction equation
Cl.[NH2:2][CH2:3][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].[F:24][C:25]([F:37])([F:36])[O:26][C:27]1[CH:35]=[CH:34][C:30]([C:31](Cl)=[O:32])=[CH:29][CH:28]=1.C(N(CC)C(C)C)(C)C>C(#N)C>[O:22]=[C:16]1[CH:15]([N:8]2[C:7](=[O:23])[C:6]3[C:11](=[CH:12][CH:13]=[C:4]([CH2:3][NH:2][C:31](=[O:32])[C:30]4[CH:34]=[CH:35][C:27]([O:26][C:25]([F:24])([F:36])[F:37])=[CH:28][CH:29]=4)[CH:5]=3)[N:10]=[C:9]2[CH3:14])[CH2:20][CH2:19][C:18](=[O:21])[NH:17]1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 1421104-(Trifluoromethoxy)benzoyl ChlorideHCID 687303673-(6-(aminomethyl)-2-methyl-4-oxoquinazolin-3(4H)-yl)piperidine-2,6-dione hydrochloride

Product 1

HCID 25235825HCID 25235825, compoundYield 73.1%

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 (0.49 g, 1.4 mmol) in acetonitrile (10 mL), was added 4-trifluoromethoxy-benzoyl chloride (0.34 mL, 2.2 mmol) and N,N-diisopropyl ethylamine (0.63 mL, 3.6 mmol). The mixture was stirred at room temperature for one hour. 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-6-ylmethyl]-4-trifluoromethoxy-benzamide as an off-white solid (500 mg, 71% 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, 6.40 min (99.5%); mp, 165-167° C.; 1HNMR (DMSO-d6) 2.15-2.20 (m, 1H, CHH), 2.56-2.88 (m, 6H, CHCH2, CH3), 4.60 (d, J=5 Hz, 2H, CH2NH), 5.26 (dd, J=6, 11 Hz, 1H, CH), 7.458-8.04 (m, 7H, Ar), 9.28 (t, J=5 Hz, 1H, CH2NH), 11.02 (s, 1H, NH); 13C NMR (DMSO-d6) δ 20.90, 23.40, 30.60, 42.35, 56.53, 119.93 (q, JC-F=257 Hz), 120.01, 120.67, 123.87, 126.62, 129.56, 133.19, 134.17, 134.07, 137.97, 145.83, 150.35, 154.61, 160.43, 165.06, 169.45, 172.59. LCMS MH=489; Anal Calcd For C23H19N4O5F3+1.1H2O: C, 54.36; H. 4.20; N, 11.02; F, 11.21. Found: C, 54.40; H, 3.89; N, 10.67; F, 11.06.

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-92c06911ad6240989f7de9002e9af70f
Source dataset
uspto-grants-2013_07
Patent number
US08492395B2

Reaction notes

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