1-Isopropylpiperazine → HCID 136248828, compound

HRID 922354Notes

Reaction equation

HRID 922354 reaction equation
Br[C:2]1[CH:3]=[C:4]([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:6][CH:7]=1.[CH:23]([N:26]1[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]1)([CH3:25])[CH3:24].CC(C)([O-])C.[K+].C1(P(C2C=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>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH:23]([N:26]1[CH2:31][CH2:30][N:29]([C:2]2[CH:3]=[C:4]([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:6][CH:7]=2)[CH2:28][CH2:27]1)([CH3:25])[CH3:24]

Participants

6

Reactant 4

HCID 780131-IsopropylpiperazineHCID 634876Binap, (A+-)-HCID 23665647Potassium tert-butoxideHCID 136408147HCID 136408147, compound

Product 1

HCID 136248828HCID 136248828, compoundYield 14.2%

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
100 °C

Procedure

A mixture of 2-(3-bromo-phenyl)-5,7-dimethoxy-3H-quinazolin-4-one (0.5 g, 1.38 mmol), 1-isopropyl-piperazine (0.24 mL, 1.66 mmol), potassium t-butoxide (0.32 g, 3.31 mmol), 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (60.1 mg, 0.096 mmol) and tris(dibenzylideneacetone)dipalladium(0) (31.6 mg, 0.034 mmol) in nitrogen saturated toluene (10 mL) was heated at 100° C. for 48 h. After that time the reaction was cooled to rt and concentrated under reduced pressure. The product was purified by flash column chromatography (silica gel, dichloromethane to 97:3 dichloromethane/methanol) to give 2-(3-(4-isopropylpiperazin-1-yl)phenyl)-5,7-dimethoxyquinazolin-4(3H)-one (0.080 g, 14%) as a yellow solid: mp 251-253° C.; 1H NMR (400 MHz, CDCl3): δ 7.56 (s, 1H), 7.42-7.38 (m, 2H), 7.13-7.09 (m, 1H), 6.84 (d, J=2.4 Hz, 1H), 6.46 (d, J=2.4 Hz, 1H), 3.98 (s, 3H), 3.94 (s, 3H), 3.38-3.28 (m, 4H), 2.78-2.68 (m, 4H), 1.11 (d, 6H); ESI MS m/z 407 (M−1)−

Workup

  1. temperatureAfter that time the reaction was cooled to rt
  2. concentrationconcentrated under reduced pressure
  3. customThe product was purified by flash column chromatography (silica gel, dichloromethane to 97:3 dichloromethane/methanol)

Sources & evidence

ORD record
ord-7559fcadab6a4bbe80360c0cbce7d81f
Source dataset
uspto-grants-2016_03
Patent number
US09278940B2

Reaction notes

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