Triethylamine → 4-[(3-Bromophenyl)amino]-7-[3-(1-methylpiperidin-4-yl)propyloxy]-6-[(vinylcarbonyl)amino]quinazoline

HRID 1023293Notes

Reaction equation

HRID 1023293 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[O:12][CH2:13][CH2:14][CH2:15][CH:16]1[CH2:21][CH2:20][N:19]([CH3:22])[CH2:18][CH2:17]1)[N:8]=[CH:7][N:6]=[C:5]2[NH:23][C:24]1[CH:29]=[CH:28][CH:27]=[C:26]([Br:30])[CH:25]=1.C(N(CC)CC)C.[C:38](Cl)(=[O:41])[CH:39]=[CH2:40]>ClCCl.O1CCCC1>[Br:30][C:26]1[CH:25]=[C:24]([NH:23][C:5]2[C:4]3[C:9](=[CH:10][C:11]([O:12][CH2:13][CH2:14][CH2:15][CH:16]4[CH2:21][CH2:20][N:19]([CH3:22])[CH2:18][CH2:17]4)=[C:2]([NH:1][C:38]([CH:39]=[CH2:40])=[O:41])[CH:3]=3)[N:8]=[CH:7][N:6]=2)[CH:29]=[CH:28][CH:27]=1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 13140Acryloyl chlorideHCID 111906016-Amino-4-[(3-bromophenyl)amino]-7-[3-(1-methylpiperidin-4-yl)propyloxy]quinazoline

Product 1

HCID 114098744-[(3-Bromophenyl)amino]-7-[3-(1-methylpiperidin-4-yl)propyloxy]-6-[(vinylcarbonyl)amino]quinazoline

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-10 °C

Procedure

To a solution of 300 mg of 6-amino-4-[(3-bromophenyl)amino]-7-[3-(1-methylpiperidin-4-yl)propyloxy]quinazoline in 7 ml of dichloromethane are added 0.28 ml of triethylamine. The reaction mixture is cooled to about −10° C. in an ice/sodium chloride cooling bath. Then a solution of 59 μl of acrylic acid chloride in 1 ml of tetrahydrofuran is added dropwise within 10 minutes. The cooling bath is removed and the mixture is stirred for a further 15 minutes at ambient temperature. For working up, the reaction mixture is poured on to 20 ml of ice water and mixed with 2-3 ml of 2 N sodium hydroxide solution, whereupon a light-colored precipitate is formed. The precipitate is suction filtered, washed with cold water and dissolved in dichloromethane. The solution is dried over sodium sulfate and concentrated by evaporation. The resin-like crude product is purified by chromatography over a silica gel column with methylene chloride/methanol/concentrated ammonia solution (90:10:0.5). Yield: 118 mg (35% of theory); Rf value: 0.35 (silica gel, methylene chloride/methanol/concentrated aqueous ammonia solution=90:10:0.1); mass spectrum (ESI+): m/z=524, 526 [M+H]+.

Workup

  1. customThe cooling bath is removed
  2. additionthe reaction mixture is poured on to 20 ml of ice water
  3. additionmixed with 2-3 ml of 2 N sodium hydroxide solution, whereupon a light-colored precipitate
  4. customis formed
  5. filtrationfiltered
  6. washwashed with cold water
  7. dissolutiondissolved in dichloromethane
  8. dry with materialThe solution is dried over sodium sulfate
  9. concentrationconcentrated by evaporation
  10. customThe resin-like crude product is purified by chromatography over a silica gel column with methylene chloride/methanol/concentrated ammonia solution (90:10:0.5)

Sources & evidence

ORD record
ord-bae2baedb3354cdca66ea762a50c8a3e
Source dataset
uspto-grants-2014_05
Patent number
US08722694B2

Reaction notes

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