Hydrochloric Acid → (4-Benzyloxy-phenyl)-(-6-(3-methylisoxazol-5-yl)-quinazolin-4-yl)-amine hydrochloride

HRID 1936809Notes

Reaction equation

HRID 1936809 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([NH:15][C:16]2[C:25]3[C:20](=[CH:21][CH:22]=[C:23]([C:26]#[CH:27])[CH:24]=3)[N:19]=[CH:18][N:17]=2)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[N+:28]([CH2:31][CH3:32])([O-])=[O:29].C1(N=C=O)C=CC=CC=1.[ClH:42]>C(N(CC)CC)C.C(OCC)(=O)C.ClCCl>[ClH:42].[CH2:1]([O:8][C:9]1[CH:10]=[CH:11][C:12]([NH:15][C:16]2[C:25]3[C:20](=[CH:21][CH:22]=[C:23]([C:26]4[O:29][N:28]=[C:31]([CH3:32])[CH:27]=4)[CH:24]=3)[N:19]=[CH:18][N:17]=2)=[CH:13][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 6587NitroethaneHCID 7672Phenyl isocyanateHCID 22609768(4-Benzyloxy-phenyl)(6-ethynylquinazolin-4-yl)-amine

Product 1

HCID 22609788(4-Benzyloxy-phenyl)-(-6-(3-methylisoxazol-5-yl)-quinazolin-4-yl)-amine hydrochlorideYield 11%

Reagents, catalysts & solvents 3

HCID 8471TriethylamineCatalystHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A stirred mixture of (4-benzyloxy-phenyl)-(6-ethynylquinazolin-4-yl)-amine (0.20 g, 0.57 mmol), nitroethane (0.20 g, 2.7 mmol), phenylisocyanate (0.15 ml, 0.164 g, 1.38 mmol), and triethylamine (3 drops) in a mixture of ethyl acetate (10 ml) and dichloromethane (5 ml) was heated at reflux for 18 hours. After cooling the mixture was filtered to remove solid, and the concentrated filtrate was purified by silica gel chromatography, eluting with 50% ethyl acetate/i-hexane. After concentration of the appropriate fractions, the material obtained was treated with methanolic HCl, the solvent was removed in vacuo and the residue was triturated with ether to give the title compound as a yellow solid (0.027 g, 0.061 mmol, 11%); δH [2H6]DMSO 12.0 (1H,s), 9.55 (1H,s), 8.91 (1H,s), 8.48 (1H,d), 8.03 (1H,d), 7.68 (2H,d), 7.32-7.55 (5H,m), 7.22 (1H,s), 7.15 (2H,d), 5.18 (2H,s), 2.35 (3H,s); m/z (M+1+) 409.

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 18 hours
  3. temperatureAfter cooling the mixture
  4. filtrationwas filtered
  5. customto remove solid
  6. customthe concentrated filtrate was purified by silica gel chromatography
  7. washeluting with 50% ethyl acetate/i-hexane
  8. customAfter concentration of the appropriate fractions, the material obtained
  9. customthe solvent was removed in vacuo
  10. customthe residue was triturated with ether

Sources & evidence

ORD record
ord-9fb7cd1284144383ac253d6301399840
Source dataset
uspto-grants-2002_05
Patent number
US06391874B1

Reaction notes

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