N-(3-Aminopropyl)morpholine → (2R)-7-(2-hydroxy-3-(3-morpholinopropylamino)propoxy)-6-methoxy-4-(3-methylindol-5-yloxy)quinazoline

HRID 454280Notes

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]1[CH2:17][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].[NH2:29][CH2:30][CH2:31][CH2:32][N:33]1[CH2:38][CH2:37][O:36][CH2:35][CH2:34]1>CN(C=O)C>[OH:16][C@H:15]([CH2:17][NH:29][CH2:30][CH2:31][CH2:32][N:33]1[CH2:38][CH2:37][O:36][CH2:35][CH2:34]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

Conditions

Temperature: 70 °C

Procedure

A mixture of (2R)-6-methoxy-4-(3-methylindol-5-yloxy)-7-(oxiran-2-ylmethoxy)quinazoline (100 mg, 0.28 mmol), (prepared as described in Example 278), and 4-(3-aminopropyl)morpholine (0.12 ml, 0.84 mmol) in DMF (5 ml) was heated to 70° C. for 3 hours. The solvents were removed in vacuo and the residue taken up in dichloromethane. This was washed with water, dried (MgSO3), filtered and evaporated. The residue was purified by silica column chromatography using gradient elution (dichloromethane, 5% methanol/95% dichloromethane, 20% methanolic ammonia (7M)/80% dichloromethane) to give (2R)-7-(2-hydroxy-3-(3-morpholinopropylamino)propoxy)-6-methoxy-4-(3-methylindol-5-yloxy)quinazoline (67 mg, 46%).

Workup

customThe solvents were removed in vacuo
washThis was washed with water
dry with materialdried (MgSO3)
filtrationfiltered
customevaporated
customThe residue was purified by silica column chromatography
washelution (dichloromethane, 5% methanol/95% dichloromethane, 20% methanolic ammonia (7M)/80% dichloromethane)

Sources & evidence

ORD record: ord-66c56ca0bb4345d1a7b66ae0b42b8745
Source dataset: uspto-grants-2013_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08492560B2

Reaction notes

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