Triethylamine → 4-(4-bromo-2-fluorophenoxy)-6-methoxy-7-(3-(N-methylsulphonylamino)propoxy)quinazoline

HRID 454125Notes

Reaction equation

HRID 454125 reaction equation
[NH2:1][CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:15]=[C:14]2[C:9]([C:10]([O:16][C:17]3[CH:22]=[CH:21][C:20]([Br:23])=[CH:19][C:18]=3[F:24])=[N:11][CH:12]=[N:13]2)=[CH:8][C:7]=1[O:25][CH3:26].C(N(CC)CC)C.[CH3:34][S:35](Cl)(=[O:37])=[O:36]>ClCCl>[Br:23][C:20]1[CH:21]=[CH:22][C:17]([O:16][C:10]2[C:9]3[C:14](=[CH:15][C:6]([O:5][CH2:4][CH2:3][CH2:2][NH:1][S:35]([CH3:34])(=[O:37])=[O:36])=[C:7]([O:25][CH3:26])[CH:8]=3)[N:13]=[CH:12][N:11]=2)=[C:18]([F:24])[CH:19]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 220308707-(3-Aminopropoxy)-4-(4-bromo-2-fluorophenoxy)-6-methoxyquinazoline

Product 1

HCID 220307624-(4-bromo-2-fluorophenoxy)-6-methoxy-7-(3-(N-methylsulphonylamino)propoxy)quinazolineYield 93.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution of 7-(3-aminopropoxy)-4-(4-bromo-2-fluorophenoxy)-6-methoxyquinazoline (2.71 g, 6.4 mmol) and triethylamine (1.1 ml, 0.80 g, 7.9 mmol) in dichloromethane (15 ml) was treated with a solution of methanesulphonyl chloride (0.53 ml, 0.79 g, 6.9 mmol) in dichloromethane (10 ml) and stirred at ambient temperature, under nitrogen for 18 hours. The dichloromethane was then removed by evaporation and THF (4 ml) added. The resulting solution was treated with saturated aqueous sodium hydrogen carbonate solution (to pH 8), stirred vigorously for 30 minutes and the precipitate filtered, washed with water and dried to give 4-(4-bromo-2-fluorophenoxy)-6-methoxy-7-(3-(N-methylsulphonylamino)propoxy)quinazoline (2.98 g, 93%).

Workup

  1. customThe dichloromethane was then removed by evaporation and THF (4 ml)
  2. additionadded
  3. additionThe resulting solution was treated with saturated aqueous sodium hydrogen carbonate solution (to pH 8)
  4. stirringstirred vigorously for 30 minutes
  5. filtrationthe precipitate filtered
  6. washwashed with water
  7. customdried

Sources & evidence

ORD record
ord-c5c8355781964c508fefc358953ab14a
Source dataset
uspto-grants-2013_07
Patent number
US08492560B2

Reaction notes

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