Chloroacetonitrile → 7-(1-Cyanomethylpiperidin-4-ylmethoxy)-6-methoxy-4-(3-methylindol-5-yloxy)quinazoline

HRID 1791791Notes

Reaction equation

HRID 1791791 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][CH:26]=[C:25]2[CH3:31].[CH2:32]([N:34](CC)CC)[CH3:33].ClCC#N>CO>[C:32]([CH2:33][N:18]1[CH2:19][CH2:20][CH:15]([CH2:14][O:13][C:12]2[CH:11]=[C:10]3[C:5]([C:6]([O:21][C:22]4[CH:23]=[C:24]5[C:28](=[CH:29][CH:30]=4)[NH:27][CH:26]=[C:25]5[CH3:31])=[N:7][CH:8]=[N:9]3)=[CH:4][C:3]=2[O:2][CH3:1])[CH2:16][CH2:17]1)#[N:34]

Participants

5

Reactant 3

HCID 7856ChloroacetonitrileHCID 8471TriethylamineHCID 220307946-methoxy-4-[(3-methyl-1H-indol-5-yl)oxy]-7-[(piperidin-4-yl)methoxy]quinazoline

Product 1

HCID 220308947-(1-Cyanomethylpiperidin-4-ylmethoxy)-6-methoxy-4-(3-methylindol-5-yloxy)quinazolineYield 35%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A mixture of 6-methoxy-4-(3-methylindol-5-yloxy)-7-(piperidin-4-ylmethoxy)quinazoline (460 mg, 1.10 mmol), (prepared as described in Example 276), triethylamine (5 ml) and chloroacetonitrile (0.38 ml, 6.05 mmol) in methanol (5 ml) was stirred at ambient temperature for 24 hours. The solvents were removed in vacuo and the residue purified by silica column chromatography using gradient elution (dichloromethane, 5% methanol/95% dichloromethane, methanol/dichloromethane/0.880 saturated aqueous ammonia (100/8/1)) and the product recrystallised from acetonitrile to give 7-(1-cyanomethylpiperidin-4-ylmethoxy)-6-methoxy-4-(3-methylindol-5-yloxy)quinazoline (178 mg, 35%).

Workup

  1. customThe solvents were removed in vacuo
  2. customthe residue purified by silica column chromatography
  3. washelution (dichloromethane, 5% methanol/95% dichloromethane, methanol/dichloromethane/0.880 saturated aqueous ammonia (100/8/1))
  4. customthe product recrystallised from acetonitrile

Sources & evidence

ORD record
ord-af9c13b920d74909b69f5bc1fb670bf3
Source dataset
uspto-grants-2006_07
Patent number
US07074800B1

Reaction notes

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