Hexane → 6-amino-4-[(3-bromophenyl)amino]-7-[4-(N,N-dimethylamino)butyloxy]quinazoline

HRID 1698952Notes

Reaction equation

CCCCCC.[CH3:7][N:8]([CH2:10][CH2:11][CH2:12][CH2:13][OH:14])[CH3:9].[Br:15][C:16]1[CH:17]=[C:18]([NH:22][C:23]2[C:32]3[C:27](=[CH:28][C:29](F)=[C:30]([N+:33]([O-])=O)[CH:31]=3)[N:26]=[CH:25][N:24]=2)[CH:19]=[CH:20][CH:21]=1.CCOC(C)=O>C1COCC1.C(Cl)Cl.CCCCCC.CO.CCOC(C)=O>[NH2:33][C:30]1[CH:31]=[C:32]2[C:27](=[CH:28][C:29]=1[O:14][CH2:13][CH2:12][CH2:11][CH2:10][N:8]([CH3:9])[CH3:7])[N:26]=[CH:25][N:24]=[C:23]2[NH:22][C:18]1[CH:19]=[CH:20][CH:21]=[C:16]([Br:15])[CH:17]=1

Participants

Conditions

Temperature: 20 °C

Procedure

To a suspension of hexane prewashed sodium hydride (11.0 mmol, 440 mg of a 60% dispersion in mineral oil) in THF (20 mL) was cannulated a solution of 4-(N,N-dimethylamino)butan-1-ol (8.80 mmol, 1.03 g) in THF (30 mL). The resulting suspension was stirred at 20° C. under N2 for 2 hours and then cannulated into a solution of 4-[(3-bromophenyl)amino]-7-fluoro-6-nitroquinazoline (J Med Chem, 1996;39:918-928) (0.80 g, 2.20 mmol) in THF (30 mL) under N2. The dark red solution was then heated at reflux overnight. Identical workup as above gave, after chromatography on grade III alumina eluting with EtOAc to MeOH/EtOAc (5:95) to give 6-amino-4-[(3-bromophenyl)amino]-7-[4(N,N-dimethylamino)butyloxy]quinazoline (310 mg, 33%) as a pale brown powder, mp (CH2Cl2/hexane) 155-156° C.

Workup

temperatureThe dark red solution was then heated
temperatureat reflux overnight
customIdentical workup as above gave

Sources & evidence

ORD record: ord-338a8fee1d5d47ad95776c56a158f484
Source dataset: uspto-grants-2002_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06344459B1

Reaction notes

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