2-(Tributylstannyl)pyrazine → 1,5-Anhydro-2,3-dideoxy-3-{[(4-{[6-(pyrazin-2-yl)pyridine-3-yl]methyl}-5,6,7,8-tetrahydroquinolin-2-yl)carbonyl]amino}-L-threo-pentitol

HRID 2409515Notes

Reaction equation

HRID 2409515 reaction equation
Cl[C:2]1[N:7]=[CH:6][C:5]([CH2:8][C:9]2[C:18]3[CH2:17][CH2:16][CH2:15][CH2:14][C:13]=3[N:12]=[C:11]([C:19]([NH:21][C@@H:22]3[C@@H:27]([OH:28])[CH2:26][O:25][CH2:24][CH2:23]3)=[O:20])[CH:10]=2)=[CH:4][CH:3]=1.C([Sn](CCCC)(CCCC)[C:34]1[CH:39]=[N:38][CH:37]=[CH:36][N:35]=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>[N:35]1[CH:36]=[CH:37][N:38]=[CH:39][C:34]=1[C:2]1[N:7]=[CH:6][C:5]([CH2:8][C:9]2[C:18]3[CH2:17][CH2:16][CH2:15][CH2:14][C:13]=3[N:12]=[C:11]([C:19]([NH:21][C@@H:22]3[C@@H:27]([OH:28])[CH2:26][O:25][CH2:24][CH2:23]3)=[O:20])[CH:10]=2)=[CH:4][CH:3]=1

Participants

6

Reactant 2

HCID 27373162-(Tributylstannyl)pyrazineHCID 547673451,5-anhydro-3-[({4-[(6-chloropyridin-3-yl)methyl]-5,6,7,8-tetrahydroquinolin-2-yl}carbonyl)amino]-2,3-dideoxy-L-threo-pentitol

Product 1

HCID 547675121,5-Anhydro-2,3-dideoxy-3-{[(4-{[6-(pyrazin-2-yl)pyridine-3-yl]methyl}-5,6,7,8-tetrahydroquinolin-2-yl)carbonyl]amino}-L-threo-pentitol

Reagents, catalysts & solvents 3

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

Procedure

To a solution of 1,5-anhydro-3-[({4-[(6-chloropyridin-3-yl)methyl]-5,6,7,8-tetrahydroquinolin-2-yl}carbonyl)amino]-2,3-dideoxy-L-threo-pentitol (Example 1, 0.038 g, 0.095 mmol) in 1 mL of dioxane under an atmosphere of nitrogen was added 2-(tributylstannyl)-pyrazine (0.060 mL g, 0.19 mmol) and tetrakis(triphenylphosphine)palladium(0) (0.011 g, 0.0095 mmol). The mixture was irradiated in a microwave reactor at 130° C. for 1.5 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 silica gel chromatography, eluting with 0-6% methanol in dichloromethane, to provide the title compound that gave a proton NMR spectra consistent with theory and a mass ion (ES+) of 446.0 for [M+H]+: 1H NMR (400 MHz, d6-DMSO) δ 9.52 (s, 1H), 8.74-8.70 (m, 2H), 8.64 (s, 1H), 8.34-8.30 (m, 2H), 7.77-7.66 (m, 1H), 7.63 (s, 1H), 4.16 (s, 2H), 3.82-3.72 (m, 3H), 3.69-3.53 (m, 1H), 3.04-2.99 (m, 1H), 2.92 (br s, 2H), 2.75 (br s, 2H), 1.96-1.66 (m, 4H), 1.65-1.55 (m, 2H), 1.13-1.09 (m, 1H).

Workup

  1. customThe mixture was irradiated in a microwave reactor at 130° C. for 1.5 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 silica gel chromatography
  7. washeluting with 0-6% methanol in dichloromethane

Sources & evidence

ORD record
ord-42b32563ec5148809c70546ef1b90093
Source dataset
uspto-grants-2014_08
Patent number
US08815902B2

Reaction notes

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