Methanol → 3-[(1S,2S)-2-Hydroxycyclohexyl]-6-[(6-methoxypyridin-3-yl)methyl]pyrido[3,4-h]quinazolin-4(3H)-one

HRID 1183822Notes

Reaction equation

Cl[C:2]1[N:7]=[CH:6][C:5]([CH2:8][C:9]2[CH:10]=[C:11]3[C:16](=[C:17]4[CH:22]=[CH:21][N:20]=[CH:19][C:18]=24)[N:15]=[CH:14][N:13]([C@H:23]2[CH2:28][CH2:27][CH2:26][CH2:25][C@@H:24]2[OH:29])[C:12]3=[O:30])=[CH:4][CH:3]=1.CN[C@@H]1CCCC[C@H]1NC.[CH3:41][OH:42]>[Cu]I>[OH:29][C@H:24]1[CH2:25][CH2:26][CH2:27][CH2:28][C@@H:23]1[N:13]1[C:12](=[O:30])[C:11]2[C:16](=[C:17]3[CH:22]=[CH:21][N:20]=[CH:19][C:18]3=[C:9]([CH2:8][C:5]3[CH:6]=[N:7][C:2]([O:42][CH3:41])=[CH:3][CH:4]=3)[CH:10]=2)[N:15]=[CH:14]1

Participants

Conditions

Temperature: 150 °C

Procedure

To a solution of 6-[(6-chloropyridin-3-yl)methyl]-3-[(1S,2S)-2-hydroxycyclohexyl]pyrido[3,4-h]quinazolin-4(3H)-one (Example 1, 0.060 g, 0.14 mmol) in 2 mL of methanol under an atmosphere of nitrogen was added trans-N,N′-dimethylcyclohexane-1,2-diamine (6.0 mg, 0.042 mmol) and copper(I) iodide (6.0 mg, 0.033 mmol). The mixture was heated at 150° C. for 15 h in a sealed pressure vessel, cooled to rt, and concentrated in vacuo. The residue was purified via silica gel chromatography, eluting with 0-5% methanol in dichloromethane, to provide the title compound that gave a proton NMR spectra consistent with theory and a mass ion (ES+) of 417.0 for [M+H]+: 1H NMR (400 MHz, CD3OD) δ 9.41 (s, 1H), 8.68 (s, 1H), 8.60-8.54 (m, 1H), 8.36-8.28 (m, 2H), 8.09 (s, 1H), 8.05 (s, 1H), 7.40-7.38 (m, 1H), 6.66 (d, J=8.3 Hz, 1H), 4.58 (br s, 1 H), 4.47 (s, 2H), 4.09 (br s, 1H), 3.90 (s, 3H), 2.61 (br s, 1H), 2.30-2.27 (m, 1H), 2.05-1.92 (m, 4H), 1.40-1.32 (m, 2H).

Workup

temperaturecooled to rt
concentrationconcentrated in vacuo
customThe residue was purified via silica gel chromatography
washeluting with 0-5% methanol in dichloromethane

Sources & evidence

ORD record: ord-348b7789c50a412594dbb26fd71ac5b1
Source dataset: uspto-grants-2014_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08664387B2

Reaction notes

Loading…