Triethylamine → 4-Amino-6,7-dimethoxy-2-[(+/-)-cis-octahydro-1-quinoxalinyl]-quinazoline dihydrochloride

HRID 967013Notes

Reaction equation

HRID 967013 reaction equation
[NH2:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:14][CH3:15])=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[C:4]([Cl:16])[N:3]=1.C(N(CC)CC)C.[NH:24]1[C@@H:33]2[C@@H:28]([CH2:29][CH2:30][CH2:31][CH2:32]2)[NH:27][CH2:26][CH2:25]1>CN(C1C=CC=CN=1)C.CC(CCO)C>[ClH:16].[ClH:16].[NH2:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:14][CH3:15])=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[C:4]([N:24]2[C@@H:33]3[C@@H:28]([CH2:29][CH2:30][CH2:31][CH2:32]3)[NH:27][CH2:26][CH2:25]2)[N:3]=1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 902352-Chloro-6,7-dimethoxy-4-quinazolinamineHCID 15650612HCID 15650612, compound

Product 1

HCID 865863104-Amino-6,7-dimethoxy-2-[(+/-)-cis-octahydro-1-quinoxalinyl]-quinazoline dihydrochlorideYield 215.6%

Reagents, catalysts & solvents 2

HCID 218852-DimethylaminopyridineCatalystHCID 31260Isoamyl AlcoholSolvent

Procedure

A mixture of 7.85 g of 4-amino-2-chloro-6,7-dimethoxyquinazoline, 13.3 g of triethylamine, 0.4 g of dimethylaminopyridine, 11.5 g of cis-decahydroquinoxaline and 80 ml of i-amyl alcohol was stirred at reflux for 72 hours. After cooling to room temperature, the solvent was evaporated off and the residue was purified by flash chromatography, eluting with petroleum ether:ethyl acetate:methanol:28% ammonium hydroxide 8:6:2:0.2. The obtained residue obtained was transformed into the hydrochloride salt and crystallized from i-propanol/methanol 1:1 to give 14.7 g (73%) of the desired compound; m.p. 290-295° C.

Workup

  1. temperatureat reflux for 72 hours
  2. customthe solvent was evaporated off
  3. customthe residue was purified by flash chromatography
  4. washeluting with petroleum ether
  5. customThe obtained residue obtained
  6. customcrystallized from i-propanol/methanol 1:1

Sources & evidence

ORD record
ord-a8ea2bb610f1474cb9167b2a8aa7175e
Source dataset
uspto-grants-2005_10
Patent number
US06953800B2

Reaction notes

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