Phosphorus oxychloride → 4-Chloro-7-(3-chloropropoxy)-6-methoxyquinazoline

HRID 631257

Reaction equation

HRID 631257 reaction equation
[Cl:1][CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:15]=[C:14]2[C:9]([C:10](O)=[N:11][CH:12]=[N:13]2)=[CH:8][C:7]=1[O:17][CH3:18].P(Cl)(Cl)([Cl:21])=O>C1(C)C=CC=CC=1>[Cl:21][C:10]1[C:9]2[C:14](=[CH:15][C:6]([O:5][CH2:4][CH2:3][CH2:2][Cl:1])=[C:7]([O:17][CH3:18])[CH:8]=2)[N:13]=[CH:12][N:11]=1

Participants

4

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 1784867697-(3-chloropropoxy)-6-methoxy-1H-quinazolin-4-one

Product 1

HCID 574472274-Chloro-7-(3-chloropropoxy)-6-methoxyquinazolineYield 78%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
125 °C

Procedure

To a solution of the intermediate from Step 4 (3.00 g, 11.16 mmol) in toluene (30 mL) in a pressure vessel was added phosphorous oxychloride (8 mL). The mixture was heated to 125° C. for 5 hours. Completion of the reaction was monitored by LCMS. The mixture was concentrated to dryness and excess ethyl acetate was added. The solution was washed with water and brine and was dried (Na2SO4) and concentrated to afford the pure compound 4-chloro-7-(3-chloro-propoxy)-6-methoxy-quinazoline (2.51 g, 78%) as a yellow solid. 1H NMR (300 MHz, DMSO-d6) δ 8.85 (s, 1H), 7.48 (s, 1H), 7.35 (s, 1H), 4.35 (t, 2H), 4.00 (s, 3H), 3.75 (t, 2H), 2.25 (q, 2H). LC-MS (ESI)m/z 287 (M+H)+.

Workup

  1. concentrationThe mixture was concentrated to dryness and excess ethyl acetate
  2. additionwas added
  3. washThe solution was washed with water and brine
  4. dry with materialwas dried (Na2SO4)
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-bd76335f28a84b6c96c4d33b08f4f83e
Source dataset
uspto-grants-2016_04
Patent number
US09320739B2

Linked notes

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