3,4,5-Trimethoxyaniline → HCID 76684063, compound

HRID 918910Notes

Reaction equation

HRID 918910 reaction equation
[CH2:1]([N:8]1[N:17]=[C:16](Cl)[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[C:9]1=[O:19])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:20][O:21][C:22]1[CH:23]=[C:24]([CH:26]=[C:27]([O:31][CH3:32])[C:28]=1[O:29][CH3:30])[NH2:25].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.CC(C)([O-])C.[K+]>C1(C)C=CC=CC=1>[CH2:1]([N:8]1[N:17]=[C:16]([NH:25][C:24]2[CH:26]=[C:27]([O:31][CH3:32])[C:28]([O:29][CH3:30])=[C:22]([O:21][CH3:20])[CH:23]=2)[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[C:9]1=[O:19])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 322853,4,5-TrimethoxyanilineHCID 634876Binap, (A+-)-HCID 23665647Potassium tert-butoxideHCID 24751992HCID 24751992, compound

Product 1

HCID 76684063HCID 76684063, compoundYield 29%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A mixture of 2-benzyl-4-chloro-2H-phthalazin-1-one (1.35 g, 5 mmol), 3,4,5-trimethoxyaniline (1.10 g, 6 mmol), bis(dibenzylideneacetone)palladium(II) (0.46 g, 0.5 mmol), 2,2′-bis(diphenylphosphino)-1,1′-binaphtyl (0.62 g, 1 mmol) and potassium tert-butoxide (0.84 g, 7.5 mmol) in anhydrous toluene (20 mL) was degassed and heated to reflux with stirring for 19 h. After that time, the mixture was cooled to rt and quenched with saturated aqueous NH4Cl (20 mL). Ethyl acetate (20 mL) and water (20 mL) were added and the organic phase was separated, washed with brine (20 mL), dried over MgSO4 and concentrated under reduced pressure. The product was purified by flash column chromatography (silica gel, 60:40 hexanes/ethyl acetate) followed by recrystallization from CHCl3/hexanes to give 2-benzyl-4-((3,4,5-trimethoxyphenyl)amino)phthalazin-1(2H)-one (0.598 g, 29%) as a white solid: mp 206-207° C.; 1H H NMR (400 MHz, CDCl3) δ 8.57-8.55 (m, 1H), 7.84-7.76 (m, 3H), 7.41 (d, J=6.8 Hz, 2H), 7.32-7.22 (m, 3H), 6.69 (s, 2H), 6.40 (s, 1H), 5.38 (s, 2H), 3.81 (s, 3H), 3.70 (s, 6H); ESI MS m/z 418 [M+1]+.

Workup

  1. customwas degassed
  2. temperatureheated
  3. temperatureto reflux
  4. customquenched with saturated aqueous NH4Cl (20 mL)
  5. additionEthyl acetate (20 mL) and water (20 mL) were added
  6. customthe organic phase was separated
  7. washwashed with brine (20 mL)
  8. dry with materialdried over MgSO4
  9. concentrationconcentrated under reduced pressure
  10. customThe product was purified by flash column chromatography (silica gel, 60:40 hexanes/ethyl acetate)
  11. customfollowed by recrystallization from CHCl3/hexanes

Sources & evidence

ORD record
ord-7a9bf8636c0244f7b25c0b0f6243bdac
Source dataset
uspto-grants-2016_03
Patent number
US09271978B2

Reaction notes

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