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

HRID 2227942Notes

Reaction equation

HRID 2227942 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

6

Reactant 4

HCID 104483-(Methylthio)-1-propanolHCID 13831TributylphosphineHCID 730421,1'-(Azodicarbonyl)dipiperidineHCID 1355038524-[(4-Bromo-2-fluorophenyl)amino]-6-methoxy-7-quinazolinol

Product 1

HCID 224782814-(4-Bromo-2-fluoroanilino)-6-methoxy-7-(3-methylthiopropoxy)quinazolineYield 50%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
5 °C

Procedure

1,1′-(Azodicarbony)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

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

Sources & evidence

ORD record
ord-64c20125535a4f9ba9a307df06ad3328
Source dataset
uspto-grants-2002_07
Patent number
US06414148B1

Reaction notes

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