Morpholine → HCID 53261550, compound

HRID 1183831Notes

Reaction equation

HRID 1183831 reaction equation
Br[C:2]1[CH:30]=[CH:29][C:5]([CH2:6][C:7]2[CH:8]=[C:9]3[C:14](=[C:15]4[CH:20]=[CH:19][N:18]=[CH:17][C:16]=24)[N:13]=[CH:12][N:11]([C@H:21]2[CH2:26][CH2:25][CH2:24][CH2:23][C@@H:22]2[OH:27])[C:10]3=[O:28])=[CH:4][CH:3]=1.[NH:31]1[CH2:36][CH2:35][O:34][CH2:33][CH2:32]1.CC(C)([O-])C.[K+]>C1(C)C=CC=CC=1.C(OCC)(=O)C.CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C>[OH:27][C@H:22]1[CH2:23][CH2:24][CH2:25][CH2:26][C@@H:21]1[N:11]1[C:10](=[O:28])[C:9]2[C:14](=[C:15]3[CH:20]=[CH:19][N:18]=[CH:17][C:16]3=[C:7]([CH2:6][C:5]3[CH:29]=[CH:30][C:2]([N:31]4[CH2:36][CH2:35][O:34][CH2:33][CH2:32]4)=[CH:3][CH:4]=3)[CH:8]=2)[N:13]=[CH:12]1

Participants

7

Reactant 3

HCID 8083MorpholineHCID 23665647Potassium tert-butoxideHCID 68379797HCID 68379797, compound

Product 1

HCID 53261550HCID 53261550, compound

Reagents, catalysts & solvents 3

HCID 178418851HCID 178418851, compoundCatalystHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 6-(4-bromobenzyl)-3-[(1S,2S)-2-hydroxycyclohexyl]pyrido[3,4-h]quinazolin-4(3H)-one (0.050 g, 0.11 mmol) in 1 mL of toluene under an atmosphere of nitrogen was added morpholine (0.038 g, 0.43 mmol), bis(tri-tert-butylphosphine)palladium(0) (2.8 mg, 0.0054 mmol), and potassium tert-butoxide (0.030 g, 0.27 mmol). The mixture was heated to 100° C. for 18 h, cooled to rt, and diluted with ethyl acetate. The organic solution was washed with saturated aqueous sodium bicarbonate and brine, dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified via preparative reverse phase HPLC to provide the title compound that gave a proton NMR spectra consistent with theory and a mass ion (ES+) of 471.0 for [M+H]+: 1H NMR (400 MHz, d6-DMSO) δ 9.70 (s, 1H), 9.20 (d, J=6.1 Hz, 1H), 8.77 (d, J=6.2 Hz, 1H), 8.65 (s, 1H), 8.28 (s, 1H), 7.22 (d, J=8.6 Hz, 2H), 7.02 (d, J=8.6 Hz, 2H), 4.64 (s, 2H), 4.22 (br s, 1H), 3.84 (t, J=4.8 Hz, 4H), 3.18 (t, J=4.6 Hz, 4H), 2.20 (br s, 1H), 2.03-1.87 (m, 1H), 1.87-1.72 (m, 4H), 1.56-1.47 (m, 3H).

Workup

  1. temperaturecooled to rt
  2. washThe organic solution was washed with saturated aqueous sodium bicarbonate and brine
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified via preparative reverse phase HPLC

Sources & evidence

ORD record
ord-6b254c6318c04d97969f5005b82faae5
Source dataset
uspto-grants-2014_03
Patent number
US08664387B2

Reaction notes

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