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

HRID 922394Notes

Reaction equation

HRID 922394 reaction equation
Cl.[CH3:2][O:3][C:4]1[CH:13]=[C:12](OC)[CH:11]=[C:10]2[C:5]=1[C:6](=[O:29])[NH:7]C(C1C=CC=C(N3CCN(C)CC3)N=1)=[N:9]2.[CH:30]([N:33]1[CH2:38][CH2:37][N:36]([C:39]2[N:44]=[C:43]([CH:45]=O)[CH:42]=[CH:41][CH:40]=2)[CH2:35][CH2:34]1)([CH3:32])[CH3:31].C[C:48]1[CH:49]=[CH:50][C:51](S(O)(=O)=O)=[CH:52][CH:53]=1.OS([O-])=O.[Na+]>CC(N(C)C)=O.C([O-])(O)=O.[Na+]>[CH:30]([N:33]1[CH2:34][CH2:35][N:36]([C:39]2[N:44]=[C:43]([C:45]3[NH:7][C:6](=[O:29])[C:5]4[C:10](=[CH:11][C:12]([C:48]5[CH:49]=[CH:50][CH:51]=[CH:52][CH:53]=5)=[CH:13][C:4]=4[O:3][CH3:2])[N:9]=3)[CH:42]=[CH:41][CH:40]=2)[CH2:37][CH2:38]1)([CH3:31])[CH3:32]

Participants

7

Reactant 4

HCID 6101p-Toluenesulfonic acidHCID 23665763Sodium BisulfiteHCID 867193586-(4-Isopropylpiperazin-1-yl)picolinaldehydeHCID 1362488545,7-Dimethoxy-2-(6-(4-methylpiperazin-1-yl)pyridin-2-yl)quinazolin-4(3H)-one Hydrochloride

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-9878080a15ce478abc08b0e39e6f2b00
Source dataset
uspto-grants-2016_03
Patent number
US09278940B2

Reaction notes

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