Dimethylformamide → (2R)-7-(2-hydroxy-3-(4-methylpiperazin-1-yl)propoxy)-6-methoxy-4-(3-methylindol-5-yloxy)quinazoline

HRID 454275Notes

Reaction equation

HRID 454275 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][C@H:15]1C[O:16]1)[N:9]=[CH:8][N:7]=[C:6]2[O:18][C:19]1[CH:20]=[C:21]2[C:25](=[CH:26][CH:27]=1)[NH:24][CH:23]=[C:22]2[CH3:28].[CH3:29][N:30]1[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]1.[CH3:36]N(C=O)C>>[OH:16][C@H:15]([CH2:29][N:30]1[CH2:35][CH2:34][N:33]([CH3:36])[CH2:32][CH2:31]1)[CH2:14][O:13][C:12]1[CH:11]=[C:10]2[C:5]([C:6]([O:18][C:19]3[CH:20]=[C:21]4[C:25](=[CH:26][CH:27]=3)[NH:24][CH:23]=[C:22]4[CH3:28])=[N:7][CH:8]=[N:9]2)=[CH:4][C:3]=1[O:2][CH3:1]

Participants

4

Reactant 3

HCID 6228DimethylformamideHCID 531671-MethylpiperazineHCID 54069082(2R)-6-methoxy-4-(3-methylindol-5-yloxy)-7-(oxiran-2-ylmethoxy)quinazoline

Product 1

HCID 56995641(2R)-7-(2-hydroxy-3-(4-methylpiperazin-1-yl)propoxy)-6-methoxy-4-(3-methylindol-5-yloxy)quinazolineYield 80%

Conditions

Temperature
60 °C

Procedure

A mixture of (2R)-6-methoxy-4-(3-methylindol-5-yloxy)-7-(oxiran-2-ylmethoxy)quinazoline (350 mg, 0.93 mmol), (prepared as described in Example 278), and 1-methylpiperazine (0.31 ml, 2.78 mmol) in DMF (5 ml) was stirred at 60° C. for 24 hours and allowed to cool to ambient temperature. 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)) to give (2R)-7-(2-hydroxy-3-(4-methylpiperazin-1-yl)propoxy)-6-methoxy-4-(3-methylindol-5-yloxy)quinazoline (352 mg, 80%).

Workup

  1. temperatureto cool to ambient temperature
  2. customThe solvents were removed in vacuo
  3. customthe residue purified by silica column chromatography
  4. washelution (dichloromethane, 5% methanol/95% dichloromethane, methanol/dichloromethane/0.880 saturated aqueous ammonia (100/8/1))

Sources & evidence

ORD record
ord-552ca84669624ee3adb94c56993b6b7d
Source dataset
uspto-grants-2013_07
Patent number
US08492560B2

Reaction notes

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