3-(Methylthio)-1-propanol → 4-(4-Bromo-2-fluoroanilino)-6-methoxy-7-(3-methylthiopropoxy)quinazoline

HRID 1838561

Reaction equation

N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O.[CH3:19][S:20][CH2:21][CH2:22][CH2:23][OH:24].[Br:25][C:26]1[CH:45]=[CH:44][C:29]([NH:30][C:31]2[C:40]3[C:35](=[CH:36][C:37](O)=[C:38]([O:41][CH3:42])[CH:39]=3)[N:34]=[CH:33][N:32]=2)=[C:28]([F:46])[CH:27]=1.C(P(CCCC)CCCC)CCC>C(Cl)Cl>[Br:25][C:26]1[CH:45]=[CH:44][C:29]([NH:30][C:31]2[C:40]3[C:35](=[CH:36][C:37]([O:24][CH2:23][CH2:22][CH2:21][S:20][CH3:19])=[C:38]([O:41][CH3:42])[CH:39]=3)[N:34]=[CH:33][N:32]=2)=[C:28]([F:46])[CH:27]=1

Participants

Conditions

Temperature: 5 °C

Procedure

1,1′-(Azodicarbonyl)dipiperidine (1.56 g, 6.2 mmol) followed by 3-(methylthio)-1-propanol (0.32 ml, 3 mmol) was added to a mixture of 4-(4-bromo-2-fluoroanilino)-7-hydroxy-6-methoxyquinazoline (225 mg, 7.0 mmol), (prepared as described for the starting material in Example 48), and tributylphosphine (1.42 ml, 6.1 mmol) in methylene chloride (20 ml) at 5° C. The mixture was stirred at 5° C. for 1 hour and then for 18 hours at ambient temperature. The insolubles were removed by filtration and the volatiles were removed from the filtrate by evaporation. The residue was purified by column chromatography eluting with ethyl acetate/methanol (100/0 increasing to 95/5) to give 4-(4-bromo-2-fluoroanilino)-6-methoxy-7-(3-methylthiopropoxy)quinazoline (400 mg, 50%).

Workup

custom(prepared
customat 5° C
waitfor 18 hours at ambient temperature
customThe insolubles were removed by filtration
customthe volatiles were removed from the filtrate by evaporation
customThe residue was purified by column chromatography
washeluting with ethyl acetate/methanol (100/0 increasing to 95/5)

Sources & evidence

ORD record: ord-41a55bc195194d4e880b8682f146e898
Source dataset: uspto-grants-2004_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06673803B2

Linked notes

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