HomeMCPWorkbenchSkills
HomeWorkbenchNotificationsMe
llms.txt · MCP GuidePrivacy Policy · Terms of Service · Supportv1.8.0
  1. Home
  2. /Reaction

N,N-Dimethylaniline → 4-Chloro-2-(chloromethyl)quinazoline

HRID 1436268
Notes
Print preview

Reaction equation

HRID 1436268 reaction equation
[Cl:1][CH2:2][C:3]1[N:12]=[C:11](N(C2C=CC(OC)=CC=2)C)[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[N:4]=1.[Cl:23]CC1NC(=O)C2C(=CC=CC=2)N=1.P(Cl)(Cl)(Cl)=O.CN(C)C1C=CC=CC=1>C(Cl)(Cl)Cl>[Cl:23][C:11]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[N:4]=[C:3]([CH2:2][Cl:1])[N:12]=1
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

6

Reactant 4

HCID 949N,N-DimethylanilineHCID 24813Phosphorus oxychlorideHCID 11358914(2-Chloromethyl-quinazolin-4-yl)-(4-methoxy-phenyl)-methyl-amineHCID 1354173742-(chloromethyl)quinazolin-4(3H)-one

Product 1

HCID 131575204-Chloro-2-(chloromethyl)quinazoline

Reagents, catalysts & solvents 1

HCID 6212
Chloroform
Solvent

Procedure

(2-Chloromethyl-quinazolin-4-yl)-(4-methoxy-phenyl)-methyl-amine: A mixture of 2-chloromethyl-quinazolin-4(3H)-one (256 mg, 1.32 mmol), phosphoryl chloride (1.23 ml, 13.2 mmol) and N,N-dimethylaniline (0.34 ml, 2.64 mmol) in chloroform (10 ml) was heated under reflux for 4 h. The reaction mixture was poured onto ice and extracted by ethyl acetate. The solvent was evaporated, and the residue was purified by column chromatography on silica gel with acetate and hexane (1:1) as eluent, yielding 180 mg of 4-chloro-2-chloromethyl-quinazoline. The intermediate (170 mg, 0.80 mmol) and (4-methoxy-phenyl)-methylamine (131.7 mg, 0.96 mmol) in isopropyl alcohol (5 ml) with concentrated HCl (0.05 ml) was stirred at room temperature overnight. The precipitation was formed and collected by filtration, then washed and dried to give 231 mg (92%) of the title compound. 1H NMR (CDCl3): 7.82 (d, J=8.7 Hz, 1H), 7.59-7.53 (m, 1H), 7.15-7.12 (m, 2H), 7.03-7.00 (m, 2H), 6.95-6.91 (m, 2H), 4.73 (s, 2H), 3.85 (s, 3H), 3.62 (s, 3H).

Workup

  1. temperaturewas heated
  2. temperatureunder reflux for 4 h
  3. additionThe reaction mixture was poured onto ice
  4. extractionextracted by ethyl acetate
  5. customThe solvent was evaporated
  6. customthe residue was purified by column chromatography on silica gel with acetate and hexane (1:1) as eluent

Sources & evidence

ORD record
ord-43291879f11c458da704e9b360f85845
Source dataset
uspto-grants-2009_11
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US07618975B2

Reaction notes

Loading…

On this pageParticipantsProcedureWorkupSources & evidenceReaction notes