3-Morpholino-1-propanol → 4-[(3-Bromophenyl)amino]7-[(3-morpholino)propyloxy]-6-nitroquinazoline

HRID 1698782Notes

Reaction equation

[Na].[O:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][CH2:10][OH:11])[CH2:4][CH2:3]1.[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26](F)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1>C1COCC1.O>[Br:12][C:13]1[CH:14]=[C:15]([NH:19][C:20]2[C:29]3[C:24](=[CH:25][C:26]([O:11][CH2:10][CH2:9][CH2:8][N:5]4[CH2:6][CH2:7][O:2][CH2:3][CH2:4]4)=[C:27]([N+:30]([O-:32])=[O:31])[CH:28]=3)[N:23]=[CH:22][N:21]=2)[CH:16]=[CH:17][CH:18]=1

Participants

Conditions

Temperature: 20 °C

Procedure

Sodium metal (27.6 mmol, 0.63 g) was added to a solution of 3-morpholinopropan-1-ol (22.0 mmol, 3.20 g) in THF (60 mL) under N2. The resulting suspension was stirred at 20° C. for 2 hours and then cannulated into a solution of 4-[(3-bromophenyl)amino]-7-fluoro-6-nitro-quinazoline, J. Med Chem., 1996(39):918) (2.0 g, 5.51 mmol) in THF (50 mL) under N2. The solution was then heated at reflux for 24 hours before being diluted with water and extracted with EtOAc. The combined organic extracts were dried over anhydrous Na2SO4, concentrated under reduced pressure and chromatographed on alumina eluting with EtOAc/hexane (1:1) to MeOH/CH2Cl2/EtOAc (2:3:5) to give 4-[(3-bromophenyl)amino]-7-[(3-morpholino)propyloxy]-6-nitroquinazoline (1.75 g, 65%) as a yellow powder, mp (MeOH) 216-220° C.

Workup

temperatureThe solution was then heated
temperatureat reflux for 24 hours
extractionextracted with EtOAc
dry with materialThe combined organic extracts were dried over anhydrous Na2SO4
concentrationconcentrated under reduced pressure
customchromatographed on alumina eluting with EtOAc/hexane (1:1) to MeOH/CH2Cl2/EtOAc (2:3:5)

Sources & evidence

ORD record: ord-87658c17513e4acbb80fcd8963a5cf69
Source dataset: uspto-grants-2002_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06344455B1

Reaction notes

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