Phosphorus oxychloride → 4-Chloro-7-methoxy-8-(2-morpholin-4-yl-ethoxy)benzo[g]quinazoline

HRID 902431Notes

Reaction equation

HRID 902431 reaction equation
[CH3:1][O:2][C:3]1[C:4]([O:18][CH2:19][CH2:20][N:21]2[CH2:26][CH2:25][O:24][CH2:23][CH2:22]2)=[CH:5][C:6]2[CH:15]=[C:14]3[C:9]([C:10](=O)[NH:11][CH:12]=[N:13]3)=[CH:8][C:7]=2[CH:17]=1.P(Cl)(Cl)([Cl:29])=O>CCN(C1C=CC=CC=1)CC>[Cl:29][C:10]1[C:9]2[C:14](=[CH:15][C:6]3[CH:5]=[C:4]([O:18][CH2:19][CH2:20][N:21]4[CH2:26][CH2:25][O:24][CH2:23][CH2:22]4)[C:3]([O:2][CH3:1])=[CH:17][C:7]=3[CH:8]=2)[N:13]=[CH:12][N:11]=1

Participants

4

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 1363860107-methoxy-8-(2-morpholin-4-ylethoxy)-3H-benzo[g]quinazolin-4-one

Product 1

HCID 250135374-Chloro-7-methoxy-8-(2-morpholin-4-yl-ethoxy)benzo[g]quinazoline

Reagents, catalysts & solvents 1

HCID 7061N,N-DiethylanilineSolvent

Procedure

A mixture of 0.3 g (0.844 mmol) of 7-methoxy-8-(2-morpholin-4-yl-ethoxy)-3H-benzo[g]quinazolin-4-one in 8 mL of phosphorus oxychloride and 1 mL of diethylaniline is refluxed for 15 minutes. After allowing to cool to room temperature, phosphorus oxychloride and diethylaniline are removed in vacuo. A 5 mL portion of toluene is added to the crude product mixture, and the solvents are again removed in vacuo. This step is repeated one more time. The product mixture is placed in an ice bath, and to this is added 10 mL of an ice-cooled solution of saturated sodium bicarbonate. This is extracted twice with a 95:5 mixture of methylene chloride/methanol, then with 1:1 tetrahydrofuran/ethyl acetate. The organic layers are combined, dried over magnesium sulfate and concentrated in vacuo. Purification by silica gel chromatography, eluting with a solvent gradient of 98:2 to 4:1 methylene chloride/methanol, provided 0.229 g of 4-chloro-7-methoxy-8-(2-morpholin-4-yl-ethoxy)benzo[g]quinazoline as a yellow solid, mp 166-168° C.

Workup

  1. temperatureis refluxed for 15 minutes
  2. customphosphorus oxychloride and diethylaniline are removed in vacuo
  3. additionA 5 mL portion of toluene is added to the crude product mixture
  4. customthe solvents are again removed in vacuo
  5. customThe product mixture is placed in an ice bath
  6. additionto this is added 10 mL of an ice-
  7. temperaturecooled solution of saturated sodium bicarbonate
  8. extractionThis is extracted twice with a 95:5 mixture of methylene chloride/methanol
  9. dry with materialdried over magnesium sulfate
  10. concentrationconcentrated in vacuo
  11. customPurification by silica gel chromatography
  12. washeluting with a solvent gradient of 98:2 to 4:1 methylene chloride/methanol

Sources & evidence

ORD record
ord-4279436ef0e44b6dac451f229af51b89
Source dataset
uspto-grants-2008_04
Patent number
US07365197B2

Reaction notes

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