N-Ethylpiperidine → 4-Amino-6,7-dimethoxy-2-(5,6-dimethoxyisoindolin-2-yl)quinazoline

HRID 442126Notes

Reaction equation

HRID 442126 reaction equation
Cl.COC1C=C2C(=CC=1OC)CNC2.NC1C2C(=CC(OC)=C(OC)C=2)N=C(Cl)N=1.C(N1CCCCC1)C.Cl.[NH2:40][C:41]1[C:50]2[C:45](=[CH:46][C:47]([O:53][CH3:54])=[C:48]([O:51][CH3:52])[CH:49]=2)[N:44]=[C:43]([N:55]2[CH2:63][C:62]3[C:57](=[CH:58][C:59]([O:66][CH3:67])=[C:60]([O:64][CH3:65])[CH:61]=3)[CH2:56]2)[N:42]=1.[OH-].[Na+]>C(OCCO)C.C(O)C.ClCCl>[NH2:40][C:41]1[C:50]2[C:45](=[CH:46][C:47]([O:53][CH3:54])=[C:48]([O:51][CH3:52])[CH:49]=2)[N:44]=[C:43]([N:55]2[CH2:56][C:57]3[C:62](=[CH:61][C:60]([O:64][CH3:65])=[C:59]([O:66][CH3:67])[CH:58]=3)[CH2:63]2)[N:42]=1

Participants

9

Reactant 5

HCID 13007N-EthylpiperidineHCID 14798Sodium HydroxideHCID 902352-Chloro-6,7-dimethoxy-4-quinazolinamineHCID 200743501H-Isoindole, 2,3-dihydro-5,6-dimethoxy-, hydrochlorideHCID 214167044-Amino-6,7-dimethoxy-2-(5,6-dimethoxyisoindolin-2-yl)quinazoline hydrochloride

Product 1

HCID 214166944-Amino-6,7-dimethoxy-2-(5,6-dimethoxyisoindolin-2-yl)quinazoline

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 6344DichloromethaneSolventHCID 8076Glycol monoethyl etherSolvent

Procedure

A mixture consisting of the product of (B), viz., 5,6-dimethoxyisoindoline hydrochloride (1.94 g.), together with 4-amino-2-chloro-6,7-dimethoxyquinazoline (2.16 g.) and N-ethylpiperidine (3.11 g.) all dissolved in 2-ethoxyethanol (60 ml.) was refluxed for a period of six hours, followed by cooling to room temperature (~25° C.). The resulting precipitate of 4-amino-6,7-dimethoxy-2-(5,6-dimethoxyisoindolin-2-yl)quinazoline hydrochloride (3.50 g., m.p. 318° C.) was then shaken with a mixture consisting of dichloromethane (1000 ml.) and 0.5N sodium hydroxide solution in 50% aqueous ethanol (200 ml.). On separation and ultimate evaporation of the organic layer there was obtained a solid material (2.4 g.), which was subsequently crystallized from ethanol to give pure final product as the free base compound (yield, 1.40 g.), m.p. 264°-6° C.

Workup

  1. temperaturewas refluxed for a period of six hours
  2. customOn separation and ultimate evaporation of the organic layer there
  3. customwas obtained a solid material (2.4 g.), which
  4. customwas subsequently crystallized from ethanol

Sources & evidence

ORD record
ord-a623259b37084b2e8b970a00664d10d1
Source dataset
uspto-grants-1977_08
Patent number
US04044136

Reaction notes

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