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

HRID 454122Notes

Reaction equation

HRID 454122 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.Cl[CH2:33][C:34]#[N:35].C(=O)([O-])[O-].[K+].[K+].[I-].[K+]>CN(C=O)C.O>[C:34]([CH2:33][CH:14]([CH:15]1[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]1)[O:13][C:12]1[CH:11]=[C:10]2[C:5]([C:6]([O:21][C:22]3[CH:23]=[C:24]4[C:28](=[CH:29][CH:30]=3)[NH:27][C:26]([CH3:31])=[CH:25]4)=[N:7][CH:8]=[N:9]2)=[CH:4][C:3]=1[O:2][CH3:1])#[N:35]

Participants

7

Reactant 4

HCID 4875Potassium IodideHCID 7856ChloroacetonitrileHCID 11430Potassium CarbonateHCID 220308736-Methoxy-4-(2-methylindol-5-yloxy)-7-(piperidin-4-ylmethoxy)quinazoline

Product 1

HCID 220307667-((1-Cyanomethyl)piperidin-4-ylmethoxy)-6-methoxy-4-(2-methylindol-5-yloxy)quinazolineYield 66.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A mixture of 6-methoxy-4-(2-methylindol-5-yloxy)-7-(piperidin-4-ylmethoxy)quinazoline (419 mg, 1 mmol), (prepared as described in Example 70), in DMF (6 ml) containing chloroacetonitrile (114 mg, 1.5 mmol), potassium carbonate (346 mg, 2.5 mmol) and potassium iodide (50 mg, 0.3 mmol) was stirred at ambient temperature overnight. The mixture was poured into water and the precipitate was filtered, washed with water and dried under vacuum. The residue was purified by column chromatography, eluting with methylene chloride, followed by methylene chloride/methanol (98/2 and 95/5). After removal of the solvent under vacuum, the residue was triturated with ether, filtered, washed with ether and dried under vacuum to give 7-((1-cyanomethyl)piperidin-4-ylmethoxy)-6-methoxy-4-(2-methylindol-5-yloxy)quinazoline (304 mg, 66%).

Workup

  1. filtrationthe precipitate was filtered
  2. washwashed with water
  3. customdried under vacuum
  4. customThe residue was purified by column chromatography
  5. washeluting with methylene chloride
  6. customAfter removal of the solvent under vacuum
  7. customthe residue was triturated with ether
  8. filtrationfiltered
  9. washwashed with ether
  10. customdried under vacuum

Sources & evidence

ORD record
ord-d4374b64aa574b459aab1db692fd7229
Source dataset
uspto-grants-2013_07
Patent number
US08492560B2

Reaction notes

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