Butyryl chloride → HCID 24968651, compound

HRID 1409635Notes

Reaction equation

HRID 1409635 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.[C:24](Cl)(=[O:28])[CH2:25][CH2:26][CH3:27].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:24](=[O:28])[CH2:25][CH2:26][CH3:27])[N:9]=[C:8]2[CH3:14])[CH2:20][CH2:19][C:18](=[O:21])[NH:17]1

Participants

5

Reactant 3

HCID 8855Butyryl chlorideHCID 81531DiisopropylethylamineHCID 249683051015474-47-1

Product 1

HCID 24968651HCID 24968651, compoundYield 46%

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 (0.53 g, 1.6 mmol) in acetonitrile (10 mL), was added butyryl chloride (0.25 mL, 2.4 mmol) and N,N-diisopropyl ethylamine (0.65 mL, 3.9 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]-butyramide as a light yellow solid (270 mg, 46% 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, 5.18 min (98.6%); mp, 250-252° C.; 1HNMR (DMSO-d6)0.88 (t, J=7 Hz, 3H, CH3), 1.56 (m, J=7 Hz, 2H, CH2CH2CH3), 2.15-2.20 (m, 3H, CH2, CHH), 2.57-2.89 (m, 6H, CHCH2, CH3), 4.77-4.85 (m, 2H, CH2NH), 5.23 (dd, J=6, 11 Hz, 1H, CH), 7.30-7.76 (m, 3H, Ar), 8.18 (t, J=5 Hz, 1H, CH2NH), 11.02 (s, 1H, NH); 13C NMR (DMSO-d6) δ 13.65, 18.67, 20.77, 23.27, 30.58, 37.32, 41.39, 56.47, 117.63, 124.28, 125.38, 133.83, 141.23, 148.44, 154.76, 160.95, 169.51, 172.14, 172.60. LCMS MH=371; Anal Calcd For C19H22N4O4: C, 61.61; H, 5.99; N, 15.13. Found: C, 61.49; H, 5.76; N, 15.00.

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-c526034a7c5b4459bf6d9dc14c39fa26
Source dataset
uspto-grants-2014_12
Patent number
US08921385B2

Reaction notes

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