Cesium carbonate → HCID 136248837, compound

HRID 922362Notes

Reaction equation

HRID 922362 reaction equation
Br[C:2]1[N:7]=[C:6]([C:8]2[NH:17][C:16](=[O:18])[C:15]3[C:10](=[CH:11][C:12]([O:21][CH3:22])=[CH:13][C:14]=3[O:19][CH3:20])[N:9]=2)[CH:5]=[CH:4][CH:3]=1.C1(P([C:63]2[CH:68]=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[C:69](=[O:72])([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[OH:72][CH2:69][CH2:2][N:7]1[CH2:63][CH2:68][N:9]([C:2]2[N:7]=[C:6]([C:8]3[NH:17][C:16](=[O:18])[C:15]4[C:10](=[CH:11][C:12]([O:21][CH3:22])=[CH:13][C:14]=4[O:19][CH3:20])[N:9]=3)[CH:5]=[CH:4][CH:3]=2)[CH2:8][CH2:6]1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 136408149HCID 136408149, compound

Product 1

HCID 136248837HCID 136248837, compoundYield 197.2%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 312751,4-DioxaneSolvent

Procedure

To a suspension of 2-(6-bromopyridin-2-yl)-5,7-dimethoxyquinazolin-4(3H)-one (0.193 g, 0.533 mmol) in dioxane (3 mL) was added palladium(II)acetate (0.012 g, 0.053 mmol), rac-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (0.0332 g, 0.053 mmol) and cesium carbonate (0.261 g, 0.800 mmol) under nitrogen. The reaction mixture was refluxed under nitrogen for 6.5 h. After that time the reaction was cooled to rt, filtered and concentrated under reduced pressure. The residue was purified by flash column chromatography (silica gel, 95:5 dichloromethane/methanol and trace amount of ammonium hydroxide) followed by trituration with diethyl ether to give 2-(6-(4-(2-hydroxyethyl)piperazin-1-yl)pyridin-2-yl)-5,7-dimethoxyquinazolin-4(3H)-one (0.043 g, 20%) as a light yellow solid: mp 175-177° C.; 1H NMR (400 MHz, DMSO-d) δ 11.05 (br s, 1H), 7.65-7.79 (m, 2H), 7.06 (d, J=8.20 Hz, 1H), 6.78 (s, 1H), 6.58 (s, 1H), 4.48 (br s, 1H), 3.91 (s, 3H), 3.86 (s, 3H), 3.64 (br s, 4H), 3.55 (br s, 2H), 2.54 (br s, 4H), 2.45 (t, 2H); ESI MS m/z 412 [M+H]+.

Workup

  1. temperatureThe reaction mixture was refluxed under nitrogen for 6.5 h
  2. filtrationfiltered
  3. concentrationconcentrated under reduced pressure
  4. customThe residue was purified by flash column chromatography (silica gel, 95:5 dichloromethane/methanol and trace amount of ammonium hydroxide)

Sources & evidence

ORD record
ord-3e903a639b384033a36d455e04e3c0f9
Source dataset
uspto-grants-2016_03
Patent number
US09278940B2

Reaction notes

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