2-(Tributylstannyl)pyrazine → 3-[(1S,2S)-2-Hydroxycyclohexyl]-6-[(6-pyrazin-2-ylpyridin-3-yl)methyl]pyrido[3,4-h]quinazolin-4(3H)-one

HRID 1183827Notes

Reaction equation

HRID 1183827 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.C([Sn](CCCC)(CCCC)[C:36]1[CH:41]=[N:40][CH:39]=[CH:38][N:37]=1)CCC>O1CCOCC1.C(OCC)(=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[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]([C:36]4[CH:41]=[N:40][CH:39]=[CH:38][N:37]=4)=[CH:3][CH:4]=3)[CH:10]=2)[N:15]=[CH:14]1

Participants

6

Reactant 2

HCID 27373162-(Tributylstannyl)pyrazineHCID 532612286-[(6-Chloropyridin-3-yl)methyl]-3-[(1S,2S)-2-hydroxycyclohexyl]pyrido[3,4-h]quinazolin-4(3H)-one

Product 1

HCID 699265193-[(1S,2S)-2-Hydroxycyclohexyl]-6-[(6-pyrazin-2-ylpyridin-3-yl)methyl]pyrido[3,4-h]quinazolin-4(3H)-one

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

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, 0.050 g, 0.12 mmol) in 1 mL of dioxane under an atmosphere of nitrogen was added 2-(tributylstannyl)-pyrazine (0.175 g, 0.475 mmol) and tetrakis(triphenylphosphine)palladium(0) (0.014 g, 0.012 mmol). The mixture was irradiated in a microwave reactor at 160° C. for 1 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 464.9 for [M+H]: 1H NMR (400 MHz, CD3OD) δ 9.84 (s, 1H), 9.51 (s, 1H), 9.32 (d, J=6.2 Hz, 1H), 8.84 (d, J=6.2 Hz), 8.75-8.64 (m, 4H), 8.41 (d, J=8.2 Hz, 1H), 8.34 (s, 1H), 7.96-7.94 (m, 1H), 4.86 (s, 2H), 4.16 (br s, 1H), 2.19 (br s, 1H), 2.03 (br s, 1H), 1.96-1.86 (m, 3H), 1.56-1.42 (m, 4H).

Workup

  1. customThe mixture was irradiated in a microwave reactor at 160° C. for 1 h
  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-a78a723d4ca044e0994964b064abeeb4
Source dataset
uspto-grants-2014_03
Patent number
US08664387B2

Reaction notes

Loading…