4-(5-Chloro-2,3-dihydro-indol-1-yl)-6,7-dimethoxy-quinazoline → 7-Hydroxy-6-methoxyquinazoline

HRID 1597965Notes

Reaction equation

HRID 1597965 reaction equation
ClC1C=C2C(=CC=1)N([C:11]1[C:20]3[C:15](=[CH:16][C:17]([O:23]C)=[C:18]([O:21][CH3:22])[CH:19]=3)[N:14]=[CH:13][N:12]=1)CC2.Cl.[NH+]1C=CC=CC=1>>[CH3:22][O:21][C:18]1[CH:19]=[C:20]2[C:15](=[CH:16][C:17]=1[OH:23])[N:14]=[CH:13][N:12]=[CH:11]2

Participants

3

Reactant 2

HCID 189328564-(5-Chloro-2,3-dihydro-indol-1-yl)-6,7-dimethoxy-quinazolineHCID 21584435Pyridinium hydrochloride

Product 1

HCID 1360078727-Hydroxy-6-methoxyquinazolineYield 106.6%

Conditions

Temperature
170 °C

Procedure

4-(5-Chloro-2,3-dihydro-indol-1-yl)-6,7-dimethoxy-quinazoline (1.00 g, 2.93 mmol; from Example 3) was added to molten pyridinium hydrochloride (10.14 g, 88 mmol) at 170° C. The mixture was stirred at 170° C. for 0.5-1.0 hours (until <5% starting material remained by anal. RP-HPLC), and then poured into ice/water (110 mL). The precipitated orange solid was recovered by filtration, dried by azeotropic removal of H2O with CH3CN at 40° C. in vacuo, dissolved in 15% i-PrOH/CHCl3 (75 mL) and washed with saturated aqueous NaHCO3 (2×). The organic phase was dried over Na2SO4(s), filtered and concentrated in vacuo. The residue (~800 mg) was triturated with CHCl3 (60 mL) and filtered to recover the 6,7-diol (typically 200 mg, 94% purity; used without further purification)(M.P. 200° C. (dec); LC-MS: 314 (MH+); anal. RP18-HPLC RT: 4.07 min.). The filtrate was flash chromatographed on silica (40 to 80% acetone/CH2Cl2) to afford ~550 mg of the pure 6-methoxy-quinazolin-7-ol product (M.P. 175° C. (dec); LC-MS: 328 (MH+); anal. RP18-HPLC RT: 4.07 min.).

Workup

  1. filtrationThe precipitated orange solid was recovered by filtration
  2. dry with materialdried by azeotropic removal of H2O with CH3CN at 40° C. in vacuo
  3. dissolutiondissolved in 15% i-PrOH/CHCl3 (75 mL)
  4. washwashed with saturated aqueous NaHCO3 (2×)
  5. dry with materialThe organic phase was dried over Na2SO4(s)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue (~800 mg) was triturated with CHCl3 (60 mL)
  9. filtrationfiltered
  10. customto recover the 6,7-diol (typically 200 mg, 94% purity
  11. customused without further purification)(M.P. 200° C. (dec); LC-MS: 314 (MH+); anal. RP18-HPLC RT: 4.07 min.)
  12. customchromatographed on silica (40 to 80% acetone/CH2Cl2)

Sources & evidence

ORD record
ord-9b3772c047e4480581621e4823eb9834
Source dataset
uspto-grants-1998_04
Patent number
US05736534

Reaction notes

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