Calcium Carbonate → 2,2-Dimethylpropanoic acid, [6-[[(4-acetylphenyl)-2-propynylamino]methyl]-4-oxo-3(4H)-quinazolinyl]methyl ester

HRID 1722695Notes

Reaction equation

HRID 1722695 reaction equation
[CH3:1][C:2]([CH3:21])([CH3:20])[C:3]([O:5][CH2:6][N:7]1[C:16](=[O:17])[C:15]2[C:10](=[CH:11][CH:12]=[C:13]([CH2:18]Br)[CH:14]=2)[N:9]=[CH:8]1)=[O:4].[CH2:22]([NH:25][C:26]1[CH:31]=[CH:30][C:29]([C:32](=[O:34])[CH3:33])=[CH:28][CH:27]=1)[C:23]#[CH:24].C(=O)([O-])[O-].[Ca+2]>CC(N(C)C)=O>[CH3:1][C:2]([CH3:21])([CH3:20])[C:3]([O:5][CH2:6][N:7]1[C:16](=[O:17])[C:15]2[C:10](=[CH:11][CH:12]=[C:13]([CH2:18][N:25]([C:26]3[CH:27]=[CH:28][C:29]([C:32](=[O:34])[CH3:33])=[CH:30][CH:31]=3)[CH2:22][C:23]#[CH:24])[CH:14]=2)[N:9]=[CH:8]1)=[O:4]

Participants

5

Reactant 3

HCID 10112Calcium CarbonateHCID 11469351Ethanone, 1-[4-(2-propynylamino)phenyl]-HCID 136912136-Bromomethyl-3,4-dihydro-4-oxo-3-((pivaloyl)oxy)methylquinazoline

Product 1

HCID 146499992,2-Dimethylpropanoic acid, [6-[[(4-acetylphenyl)-2-propynylamino]methyl]-4-oxo-3(4H)-quinazolinyl]methyl esterYield 186.8%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
80 °C

Procedure

A suspension of 5.79 g (12.5 mmol) of 75% pure 2,2-dimethylpropanoic acid, [6-(bromomethyl)-4-oxo-3(4H)-quinazolinyl]methyl ester (European patent application 204,529), 2.89 g (16.7 mmol) of 1-[4-(2-propynylamino)phenyl]ethanone (see Example A), and 3.34 g (33.4 mmol) of dry calcium carbonate in 100 ml of dimethylacetamide (DMA) is stirred at 80° C. for eighteen hours. The suspension is poured into a water-ice mixture and stirred. The suspension is extracted with ethyl acetate. The ethyl acetate solution is dried (magnesium sulfate) and concentrated to give 10.4 g of a yellow oil. This is dissolved in a minimum amount of dichloromethane and applied to a column of 1 kg of flash silica gel packed in dichloromethane/methanol (100:1). Elution with the same solvent gives 2.83 g (50.8%) of impure product as a yellow gum followed by 2.34 g (42.0% assuming 75% pure bromomethyl compound) of the product as a cream colored foam. This is used as is without characterization in the next reaction.

Workup

  1. stirringstirred
  2. extractionThe suspension is extracted with ethyl acetate
  3. dry with materialThe ethyl acetate solution is dried (magnesium sulfate)
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-396b2db1f812405dbccb6f68348679a1
Source dataset
uspto-grants-1989_08
Patent number
US04857530

Reaction notes

Loading…