1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride → 3-[4-(3-Bromo-phenylamino)-quinazolin-7-ylcarbamoyl]acrylic acid ethyl ester

HRID 394724Notes

Reaction equation

HRID 394724 reaction equation
[NH2:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([NH:12][C:13]3[CH:18]=[CH:17][CH:16]=[C:15]([Br:19])[CH:14]=3)=[N:7][CH:8]=[N:9]2)=[CH:4][CH:3]=1.[C:20]([O:27][CH2:28][CH3:29])(=[O:26])/[CH:21]=[CH:22]/[C:23]([O-])=[O:24].Cl.CN(C)CCCN=C=NCC>CN(C)C=O>[CH2:28]([O:27][C:20](=[O:26])[CH:21]=[CH:22][C:23](=[O:24])[NH:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([NH:12][C:13]3[CH:18]=[CH:17][CH:16]=[C:15]([Br:19])[CH:14]=3)=[N:7][CH:8]=[N:9]2)=[CH:4][CH:3]=1)[CH3:29]

Participants

5

Reactant 3

HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 53280457-Amino-4-[(3-bromophenyl)amino]quinazoline2×HCID 58782252-Butenedioic acid, monoethyl ester

Product 1

HCID 537015123-[4-(3-Bromo-phenylamino)-quinazolin-7-ylcarbamoyl]acrylic acid ethyl esterYield 23.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

To an ice cold solution of 0.158 g of 7-amino-4-(3-bromoanilino)-quinazoline and 0.216 g of monoethyl fumarate in 3 mL of dry dimethylformamide was added 0.288 g of 1-(3-dimethylaminopropyl)-3-ethyl-carbodiimide HCl (EDAC). 7-Amino-4-(3-bromoanilino)-quinazoline can be made by methods well-known to those skilled in the art. See, for example, J Med Chem, 1995:3482, which is hereby incorporated by reference. After stirring at 50° C. for 5 minutes, the ice bath was removed, and the reaction was permitted to warm to room temperature where it stirred for 15 hours. The reaction was poured into cold water, and the suspension was made basic with the addition of a saturated sodium bicarbonate solution. The resulting solid was collected by filtration, washed with water, and then recrystallized from 50 mL of ethanol to afford 0.052 g of the desired product, mp >260° C.

Workup

  1. customthe ice bath was removed
  2. temperatureto warm to room temperature where it
  3. stirringstirred for 15 hours
  4. additionThe reaction was poured into cold water
  5. additionthe suspension was made basic with the addition of a saturated sodium bicarbonate solution
  6. filtrationThe resulting solid was collected by filtration
  7. washwashed with water
  8. customrecrystallized from 50 mL of ethanol

Sources & evidence

ORD record
ord-baaed05520324e13a0788dcea01f09fc
Source dataset
uspto-grants-2003_08
Patent number
US06602863B1

Reaction notes

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