Diisopropylamine → (2R)-7-(2-hydroxy-3-((N,N-diisopropyl)amino)propoxy)-4-(indol-5-yloxy)-6-methoxyquinazoline

HRID 1791813Notes

Reaction equation

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

Participants

Conditions

Temperature: 70 °C

Procedure

A mixture of (2R)-4-(indol-5-yloxy)-6-methoxy-7-(oxiran-2-ylmethoxy)quinazoline (300 mg, 0.83 mmol), (prepared as described for the starting material in Example 292), and diisopropylamine (1.35 ml, 9.7 mmol) in DMF (5 ml) was stirred at 70° C. for 19 hours under an atmosphere of nitrogen then allowed to cool to ambient temperature. The solvents were removed in vacuo and the residue purified on silica gel using gradient elution with dichloromethane, dichloromethane/methanol (95/5), dichloromethane/methanolic ammonia (7M) (98/2 to 90/10) to give (2R)-7-(2-hydroxy-3-((N,N-diisopropyl)amino)propoxy)-4-(indol-5-yloxy)-6-methoxyquinazoline (343 mg, 86%).

Workup

custom(prepared
temperatureto cool to ambient temperature
customThe solvents were removed in vacuo
customthe residue purified on silica gel using gradient elution with dichloromethane, dichloromethane/methanol (95/5), dichloromethane/methanolic ammonia (7M) (98/2 to 90/10)

Sources & evidence

ORD record: ord-1db60d30b6e54133b9e84522d2a3fd09
Source dataset: uspto-grants-2006_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07074800B1

Reaction notes

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