Potassium Iodide → 6-Methoxy-4-(2-methylindol-5-yloxy)-7-(1-(2-morpholinoethyl)piperidin-4-ylmethoxy)quinazoline

HRID 454241Notes

Reaction equation

HRID 454241 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH:15]1[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]1)[N:9]=[CH:8][N:7]=[C:6]2[O:21][C:22]1[CH:23]=[C:24]2[C:28](=[CH:29][CH:30]=1)[NH:27][C:26]([CH3:31])=[CH:25]2.[I-].[K+].Cl.Cl[CH2:36][CH2:37][N:38]1[CH2:43][CH2:42][O:41][CH2:40][CH2:39]1.C(=O)([O-])O.[Na+]>CO>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH:15]1[CH2:20][CH2:19][N:18]([CH2:36][CH2:37][N:38]3[CH2:43][CH2:42][O:41][CH2:40][CH2:39]3)[CH2:17][CH2:16]1)[N:9]=[CH:8][N:7]=[C:6]2[O:21][C:22]1[CH:23]=[C:24]2[C:28](=[CH:29][CH:30]=1)[NH:27][C:26]([CH3:31])=[CH:25]2

Participants

6

Reactant 4

HCID 4875Potassium IodideHCID 77210Morpholine, 4-(2-chloroethyl)-, hydrochloride (1:1)2×HCID 516892Sodium Bicarbonate2×HCID 220308736-Methoxy-4-(2-methylindol-5-yloxy)-7-(piperidin-4-ylmethoxy)quinazoline

Product 1

HCID 220308266-Methoxy-4-(2-methylindol-5-yloxy)-7-(1-(2-morpholinoethyl)piperidin-4-ylmethoxy)quinazolineYield 122.8%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of 6-methoxy-4-(2-methylindol-5-yloxy)-7-(piperidin-4-ylmethoxy)quinazoline (500 mg, 1.2 mmol), (prepared as described in Example 70), in methanol (11.5 ml) containing potassium iodide (99 mg, 0.6 mmol) was added 4-(2-chloroethyl)morpholine hydrochloride (134 mg, 0.72 mmol) followed by sodium hydrogen carbonate (151 mg, 1.8 mmol). After stirring for 1 hour at reflux, 4-(2-chloroethyl)morpholine hydrochloride (134 mg, 0.72 mmol) and sodium hydrogen carbonate (151 mg, 1.8 mmol) were added. After stirring 1 hour at reflux, the mixture was cooled and the precipitate was filtered, washed with methanol followed by water and dried over phosphorus pentoxide to give 6-methoxy-4-(2-methylindol-5-yloxy)-7-(1-(2-morpholinoethyl)piperidin-4-ylmethoxy)quinazoline (470 mg, 73%).

Workup

  1. temperatureat reflux
  2. stirringAfter stirring 1 hour
  3. temperatureat reflux
  4. temperaturethe mixture was cooled
  5. filtrationthe precipitate was filtered
  6. washwashed with methanol
  7. dry with materialdried over phosphorus pentoxide

Sources & evidence

ORD record
ord-ffd18bdde20f45f6864ad78494675f17
Source dataset
uspto-grants-2013_07
Patent number
US08492560B2

Reaction notes

Loading…