Potassium Carbonate → 2-(6-(4-isobutylpiperazin-1-yl)pyridin-2-yl)-5,7-dimethoxyquinazolin-4(3H)-one

HRID 1519416Notes

Reaction equation

HRID 1519416 reaction equation
F[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.C([O-])([O-])=O.[K+].[K+].[CH2:29]([N:33]1[CH2:38][CH2:37][NH:36][CH2:35][CH2:34]1)[CH:30]([CH3:32])[CH3:31].CN(C)C(=O)C>CN(C)C=O.C(OCC)(=O)C>[CH2:29]([N:33]1[CH2:38][CH2:37][N:36]([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)[CH2:35][CH2:34]1)[CH:30]([CH3:32])[CH3:31]

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 31374DimethylacetamideHCID 20520521-(2-Methylpropyl)piperazineHCID 1364081482-(6-fluoropyridin-2-yl)-5,7-dimethoxyquinazolin-4(3H)-one

Product 1

HCID 1362488332-(6-(4-isobutylpiperazin-1-yl)pyridin-2-yl)-5,7-dimethoxyquinazolin-4(3H)-oneYield 34.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
110 °C

Procedure

To a suspension of 2-(6-fluoropyridin-2-yl)-5,7-dimethoxyquinazolin-4(3H)-one (0.108 g, 0.36 mmol) in N,N-dimethylformamide (1.5 mL) was added K2CO3 (0.15 g, 1.07 mmol) and 1-isobutyl-piperazine (88.94, 0.54 mmol). The resulting mixture was heated at 110° C. for 6 h. After that time N,N-dimethylacetamide (1.5 mL) was added and heating was continued for 20 h. After that time the reaction mixture was cooled to rt, diluted with ethyl acetate and filtered. The filtrate was concentrated under reduced pressure and the residue was washed with water, and dried under high vacuum. The product was purified by flash column chromatography (silica gel, 99:1 dichloromethane/methanol) to give 2-(6-(4-isobutylpiperazin-1-yl)pyridin-2-yl)-5,7-dimethoxyquinazolin-4(3H)-one (0.052 g, 34%) as a yellow solid: mp 188-189° C.; 1H NMR (400 MHz, CDCl3) δ 10.33 (br s, 1H), 7.83 (d, J=7.42 Hz, 1H), 7.65 (dd, J=8.59, 7.42, 1H), 6.76-6.88 (m, 2H), 6.48 (d, J=2.34 Hz, 1H), 3.99 (s, 3H), 3.94 (s, 3H), 3.64 (t, J=4.88 Hz, 4H), 2.55 (t, J=4.88 Hz, 4H), 2.17 (d, J=7.42 Hz, 2H), 1.75-1.95 (m, 1H), 0.95 (d, J=6.64 Hz, 6H); ESI MS m/z 424 [M+H]+.

Workup

  1. temperatureheating
  2. temperatureAfter that time the reaction mixture was cooled to rt
  3. filtrationfiltered
  4. concentrationThe filtrate was concentrated under reduced pressure
  5. washthe residue was washed with water
  6. customdried under high vacuum
  7. customThe product was purified by flash column chromatography (silica gel, 99:1 dichloromethane/methanol)

Sources & evidence

ORD record
ord-55ed5726f27847bb9db54acf2ca4619f
Source dataset
uspto-grants-2015_07
Patent number
US09073878B2

Reaction notes

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