Dichloromethane → 2-Amino-6-(3-hydroxyprop-1-ynyl)-4-(1,3-dihydroisoindol-2-yl-carbonyl)quinazoline

HRID 1887226Notes

Reaction equation

HRID 1887226 reaction equation
C(N(CC)CC)C.[CH2:8]([OH:11])[C:9]#[CH:10].[NH2:12][C:13]1[N:22]=[C:21]([C:23]([N:25]2[CH2:33][C:32]3[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=3)[CH2:26]2)=[O:24])[C:20]2[C:15](=[CH:16][CH:17]=[C:18](I)[CH:19]=2)[N:14]=1.C(Cl)Cl>CN(C=O)C.[Cu]I.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[NH2:12][C:13]1[N:22]=[C:21]([C:23]([N:25]2[CH2:33][C:32]3[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=3)[CH2:26]2)=[O:24])[C:20]2[C:15](=[CH:16][CH:17]=[C:18]([C:10]#[C:9][CH2:8][OH:11])[CH:19]=2)[N:14]=1

Participants

8

Reactant 4

HCID 6344DichloromethaneHCID 7859Propargyl alcoholHCID 8471TriethylamineHCID 58457195(2-Amino-6-iodoquinazolin-4-yl)isoindolin-2-ylmethanone

Product 1

HCID 594834682-Amino-6-(3-hydroxyprop-1-ynyl)-4-(1,3-dihydroisoindol-2-yl-carbonyl)quinazoline

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolvent

Procedure

3 ml of triethylamine, 368.7 μl of 2-propyn-1-ol, 36.6 mg of copper(I) iodide and 67.5 mg of bis(triphenylphosphine)palladium(II) chloride (15.2% of palladium) are added to a solution of 2 g of 2-amino-6-iodo-4-(1,3-dihydroisoindol-2-ylcarbonyl)quinazoline in 3 ml of DMF under argon. The mixture is stirred at room temperature for 48 h, 100 ml of DCM are added, and the mixture is subjected to aqueous extraction a number of times. The organic phase was dried and evaporated to dryness under reduced pressure in a rotary evaporator. A little ACN is added to the residue obtained, during which a yellow solid precipitates out. Filtration and drying (drying cabinet at 40° C.) gives 1.3 g of “A964”;

Workup

  1. extractionthe mixture is subjected to aqueous extraction a number of times
  2. customThe organic phase was dried
  3. customevaporated to dryness under reduced pressure in a rotary evaporator
  4. additionA little ACN is added to the residue
  5. customobtained, during which a yellow solid
  6. customprecipitates out
  7. filtrationFiltration
  8. customdrying
  9. custom(drying cabinet at 40° C.)
  10. customgives 1.3 g of “A964”

Sources & evidence

ORD record
ord-571f6c9fe52b497bae03566b829d139b
Source dataset
uspto-grants-2013_08
Patent number
US08501754B2

Reaction notes

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