N-(3-Aminopropyl)morpholine → HCID 18176160, compound

HRID 394722Notes

Reaction equation

HRID 394722 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([NH:8][C:9]2[C:18]3[C:13](=[CH:14][C:15](F)=[CH:16][CH:17]=3)[N:12]=[CH:11][N:10]=2)[CH:5]=[CH:6][CH:7]=1.[NH2:20][CH2:21][CH2:22][CH2:23][N:24]1[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1.C([O-])(O)=O.[Na+]>CS(C)=O.O>[Br:1][C:2]1[CH:3]=[C:4]([NH:8][C:9]2[C:18]3[C:13](=[CH:14][C:15]([NH:20][CH2:21][CH2:22][CH2:23][N:24]4[CH2:29][CH2:28][O:27][CH2:26][CH2:25]4)=[CH:16][CH:17]=3)[N:12]=[CH:11][N:10]=2)[CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 61055N-(3-Aminopropyl)morpholineHCID 516892Sodium BicarbonateHCID 10615466HCID 10615466, compound

Product 1

HCID 18176160HCID 18176160, compoundYield 78%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Conditions

Temperature
110 °C

Procedure

To a solution of 4-[(3-bromophenyl)amino]-7-fluoroquinazoline (0.60 g, 1.89 mmol) in Dimethylsulfoxide (DMSO) (10 mL) was added 4-(3-aminopropyl)morpholine (7.54 mmol, 1.10 mL). The reaction mixture was heated at 110° C. for 26 hours and then diluted with water, basified by the addition of saturated NaHCO3 and then extracted with EtOAc. The combined organic extracts were washed with brine, dried over anhydrous Na2SO4, and concentrated in vacuo. Column chromatography on Grade III alumina with gradient elution from EtOAc to EtOAc/MeOH (98:2) followed by recrystallization from EtOAc/hexane gave 4-[(3-bromophenyl)amino]-7-[(3-morpholinopropyl)amino]-quinazoline (0.65 g, 78%) as cream crystals, mp 162-162.5° C.

Workup

  1. extractionextracted with EtOAc
  2. washThe combined organic extracts were washed with brine
  3. dry with materialdried over anhydrous Na2SO4
  4. concentrationconcentrated in vacuo
  5. washColumn chromatography on Grade III alumina with gradient elution from EtOAc to EtOAc/MeOH (98:2)
  6. customfollowed by recrystallization from EtOAc/hexane

Sources & evidence

ORD record
ord-c3454b6499fa46d1bb73b470a827a019
Source dataset
uspto-grants-2003_08
Patent number
US06602863B1

Reaction notes

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