p-Toluenesulfonic acid → 2-(6-(4-Isopropylpiperazin-1-yl)pyridin-2-yl)-5-methoxy-7-phenylquinazolin-4(3H)-one

HRID 1519447Notes

Reaction equation

HRID 1519447 reaction equation
[CH3:1][O:2][C:3]1[CH:12]=[C:11](OC)[CH:10]=[C:9]2[C:4]=1[C:5](=[O:33])[NH:6][C:7]([C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([N:21]3[CH2:26][CH2:25][N:24]([CH2:27][CH2:28]S(C)(=O)=O)[CH2:23][CH2:22]3)[N:16]=1)=[N:8]2.C(N1CCN([C:43]2N=[C:47]([CH:49]=O)[CH:46]=[CH:45][CH:44]=2)CC1)(C)C.[CH3:51]C1C=CC(S(O)(=O)=O)=CC=1.OS([O-])=O.[Na+]>CC(N(C)C)=O.C([O-])(O)=O.[Na+]>[CH:27]([N:24]1[CH2:23][CH2:22][N:21]([C:17]2[N:16]=[C:15]([C:7]3[NH:6][C:5](=[O:33])[C:4]4[C:9](=[CH:10][C:11]([C:43]5[CH:44]=[CH:45][CH:46]=[CH:47][CH:49]=5)=[CH:12][C:3]=4[O:2][CH3:1])[N:8]=3)[CH:20]=[CH:19][CH:18]=2)[CH2:26][CH2:25]1)([CH3:51])[CH3:28]

Participants

7

Reactant 4

HCID 6101p-Toluenesulfonic acidHCID 23665763Sodium BisulfiteHCID 867193586-(4-Isopropylpiperazin-1-yl)picolinaldehydeHCID 1362488345,7-dimethoxy-2-(6-(4-(2-(methylsulfonyl)ethyl)piperazin-1-yl)pyridin-2-yl)quinazolin-4(3H)-one

Product 1

HCID 1362488582-(6-(4-Isopropylpiperazin-1-yl)pyridin-2-yl)-5-methoxy-7-phenylquinazolin-4(3H)-oneYield 19%

Reagents, catalysts & solvents 2

HCID 31374DimethylacetamideSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
120 °C

Procedure

A solution of 3-amino-5-methoxy-[1,1′-biphenyl]-4-carboxamide (5, 0.048 g, 0.2 mmol) and 6-(4-isopropylpiperazin-1-yl)picolinaldehyde (9, 0.046 g, 0.2 mmol) in DMA (2 mL) was treated with p-TsOH (0.084 g, 0.44 mmol) and NaHSO3 (0.042 g, 0.5 mmol) and then heated at 120° C. for 3 days. After this time, the reaction mixture was cooled to room temperature, diluted with saturated NaHCO3, extracted with CH2Cl2 (2×15 mL), dried (MgSO4), filtered, and concentrated. The residue was purified by silica gel chromatography eluting with 0-20% methanol in dichloromethane to afford the title compound (0.017 g, 19%) as a white solid: 1H NMR (500 MHz, CDCl3) δ 11.16 (br s, 1H), 7.88-7.86 (m, 2H), 7.78-7.73 (m, 2H), 7.55-7.53 (m, 3H), 7.49-7.46 (m, 1H), 7.28-7.27 (m, 1H), 7.09-7.07 (m, 1H), 4.08 (s, 3H), 3.64 (br s, 4H), 2.60 (m, 1H), 2.46 (s, 4H), 0.98 (br s, 6H); ESI MS m/z 456 [M+H]+.

Workup

  1. temperatureAfter this time, the reaction mixture was cooled to room temperature
  2. extractionextracted with CH2Cl2 (2×15 mL)
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by silica gel chromatography
  7. washeluting with 0-20% methanol in dichloromethane

Sources & evidence

ORD record
ord-b4d3d0a4504f4829921e98083f1c7611
Source dataset
uspto-grants-2015_07
Patent number
US09073878B2

Reaction notes

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