Cesium carbonate → 2-(6-(4-isopropylpiperazin-1-yl)-5-methoxypyridin-2-yl)-5,7-dimethoxyquinazolin-4(3H)-one

HRID 1519429Notes

Reaction equation

HRID 1519429 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][C:3]=1[O:23][CH3:24].[CH:25]([N:28]1[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]1)([CH3:27])[CH3:26].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.C([O-])([O-])=O.[Cs+].[Cs+]>ClCCl.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH:25]([N:28]1[CH2:33][CH2:32][N:31]([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][C:3]=2[O:23][CH3:24])[CH2:30][CH2:29]1)([CH3:27])[CH3:26]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 780131-IsopropylpiperazineHCID 634876Binap, (A+-)-HCID 1364081352-(6-bromo-5-methoxypyridin-2-yl)-5,7-dimethoxyquinazolin-4(3H)-one

Product 1

HCID 1362488532-(6-(4-isopropylpiperazin-1-yl)-5-methoxypyridin-2-yl)-5,7-dimethoxyquinazolin-4(3H)-oneYield 25%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
100 °C

Procedure

To a mixture of 2-(6-bromo-5-methoxypyridin-2-yl)-5,7-dimethoxyquinazolin-4(3H)-one (0.196 g, 0.50 mmol), 1-isopropylpiperazine (0.077 g, 0.60 mmol), BINAP (0.062 g, 0.10 mmol), and Cs2CO3 (0.652 g, 2.0 mmol) in nitrogen saturated dioxane (10 mL) was added palladium(II) acetate (0.022 g, 0.10 mmol). The resulting mixture was heated at 100° C. for 3 h. After that time the reaction was cooled to rt, diluted with dichloromethane (100 mL) and washed with water (20 mL). The organic phase was dried over Na2SO4 and concentrated under reduced pressure. The product was purified by flash column chromatography (silica gel, 90:10:0.1 dichloromethane/methanol/ammonium hydroxide) to give 2-(6-(4-isopropylpiperazin-1-yl)-5-methoxypyridin-2-yl)-5,7-dimethoxyquinazolin-4(3H)-one (0.055 g, 25%) as a pale yellow solid: mp 208-210° C.; 1H NMR (400 MHz, CDCl3): δ 10.23 (br s, 1H), 8.08 (d, J=8.0 Hz, 1H), 7.17 (d, J=8.0 Hz, 1H), 6.79 (d, J=2.4 Hz, 1H), 6.45 (d, J=2.4 Hz, 1H), 3.98 (s, 3H), 3.95 (s, 3H), 3.93 (s, 3H), 3.56 (br s, 4H), 2.78 (br s, 5H), 1.15 (d, J=5.6 Hz, 6H); ESI MS m/z 440 [M+H]+.

Workup

  1. temperatureAfter that time the reaction was cooled to rt
  2. washwashed with water (20 mL)
  3. dry with materialThe organic phase was dried over Na2SO4
  4. concentrationconcentrated under reduced pressure
  5. customThe product was purified by flash column chromatography (silica gel, 90:10:0.1 dichloromethane/methanol/ammonium hydroxide)

Sources & evidence

ORD record
ord-9b5e15b509e1421b81c53dd47a10f7ef
Source dataset
uspto-grants-2015_07
Patent number
US09073878B2

Reaction notes

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