Diisopropylethylamine → HCID 24964026, compound

HRID 1409657Notes

Reaction equation

HRID 1409657 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: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: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:31](=[O:32])[C:30]3[CH:34]=[CH:35][C:27]([O:26][C:25]([F:24])([F:36])[F:37])=[CH:28][CH:29]=3)[N:9]=[C:8]2[CH3:14])[CH2:20][CH2:19][C:18](=[O:21])[NH:17]1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 1421104-(Trifluoromethoxy)benzoyl ChlorideHCID 249683051015474-47-1

Product 1

HCID 24964026HCID 24964026, compoundYield 54%

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 (0.49 g, 1.5 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 temp 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]-4-trifluoromethoxy-benzamide as a white solid (370 mg, 54% 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, 6.54 min (98.6%); mp, 258-260° C.; 1HNMR (DMSO-d6)2.18-2.23 (m, 1H, CHH), 2.59-2.92 (m, 6H, CHCH2, CH3), 4.98-5.09 (m, 2H, CH2NH), 5.26 (dd, J=6, 11 Hz, 1H, CH), 7.34-8.07 (m, 7H, Ar), 9.05 (t, J=5 Hz, 1H, CH2NH), 11.05 (s, 1H, NH); 13C NMR (DMSO-d6) δ 20.82, 23.29, 30.60, 42.22, 56.54, 117.66, 120.70, 124.15, 125.52, 129.59, 133.30, 133.96, 140.65, 148.51, 150.33, 154.84, 161.10, 165.05, 169.54, 172.63. LCMS MH=489; Anal Calcd For C23H19N4O5F3: C, 56.56; H, 3.92; N, 11.47; F, 11.67. Found: C, 56.32; H, 3.60; N, 11.23; 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-7f0284d62cb147218aa894b15d241a79
Source dataset
uspto-grants-2014_12
Patent number
US08921385B2

Reaction notes

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