Diisopropylethylamine → HCID 24963326, compound

HRID 1409643Notes

Reaction equation

HRID 1409643 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.Cl.[N:25]1[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=1[C:31](Cl)=[O:32].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]([C:26]3[CH:27]=[CH:28][CH:29]=[CH:30][N:25]=3)=[O:32])[N:9]=[C:8]2[CH3:14])[CH2:20][CH2:19][C:18](=[O:21])[NH:17]1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 135033Picolinoyl Chloride HydrochlorideHCID 249683051015474-47-1

Product 1

HCID 24963326HCID 24963326, compoundYield 10.3%

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 (0.55 g, 1.6 mmol) in acetonitrile (10 mL), was added picolinoyl chloride hydrogen chloride (0.32 g, 1.8 mmol) and N,N-diisopropyl ethylamine (0.62 mL, 3.8 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 pyridine-2-carboxylic acid [3-(2,6-dioxo-piperidin-3-yl)-2-methyl-4-oxo-3,4-dihydro-quinazolin-5-ylmethyl]-amide as an off-white solid (67 mg, 10% 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, 6.85 min (99.4%); mp, 261-263° C.; 1HNMR (DMSO-d6)2.08-2.27 (m, 1H, CHH), 2.64-2.93 (m, 6H, CHCH2, CH3), 4.91-5.05 (m, 2H, CH2NH), 5.27 (dd, J=6, 11 Hz, 1H, CH), 7.33-8.69 (m, 7H, Ar), 9.32 (t, J=6 Hz, 1H, CH2NH), 11.06 (s, 1H, NH); 13C NMR (DMSO-d6) δ 20.73, 23.31, 30.62, 42.12, 56.57, 117.72, 121.86, 125.18, 125.76, 126.60, 134.05, 137.82, 140.30, 148.55, 149.77, 154.87, 161.17, 163.79, 169.47, 172.65. LCMS MH=406; Anal Calcd For C21H19N5O4+0.5H2O: C, 60.86; H, 4.86; N, 16.90. Found: C, 60.72; H, 4.62; N, 16.69.

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-2058cbe6fa2542738de601a1cd3869e6
Source dataset
uspto-grants-2014_12
Patent number
US08921385B2

Reaction notes

Loading…