Triphenylphosphine → 7-(3-Bromopropoxy)-4-((4-fluoro-2-methyl-1H-indol-5-yl)oxy)-6-methoxyquinazoline

HRID 916402Notes

Reaction equation

HRID 916402 reaction equation
N(C(OCC)=O)=NC(OCC)=O.[F:13][C:14]1[C:22]([O:23][C:24]2[C:33]3[C:28](=[CH:29][C:30]([OH:36])=[C:31]([O:34][CH3:35])[CH:32]=3)[N:27]=[CH:26][N:25]=2)=[CH:21][CH:20]=[C:19]2[C:15]=1[CH:16]=[C:17]([CH3:37])[NH:18]2.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Br:57][CH2:58][CH2:59][CH2:60]O>C(Cl)Cl>[Br:57][CH2:58][CH2:59][CH2:60][O:36][C:30]1[CH:29]=[C:28]2[C:33]([C:24]([O:23][C:22]3[C:14]([F:13])=[C:15]4[C:19](=[CH:20][CH:21]=3)[NH:18][C:17]([CH3:37])=[CH:16]4)=[N:25][CH:26]=[N:27]2)=[CH:32][C:31]=1[O:34][CH3:35]

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 123083-Bromo-1-propanolHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 1355308324-((4-Fluoro-2-methyl-1H-indol-5-yl)oxy)-6-methoxyquinazolin-7-ol

Product 1

HCID 589602427-(3-Bromopropoxy)-4-((4-fluoro-2-methyl-1H-indol-5-yl)oxy)-6-methoxyquinazolineYield 100%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Diethyl azodicarboxylate (557 μl, 3.53 mmol) was added to a solution of 4-(4-fluoro-2-methylindol-5-yloxy)-7-hydroxy-6-methoxyquinazoline (1 g, 2.95 mmol), triphenylphosphine (1.15 g, 4.42 mmol) and 3-bromo-1-propanol (293 μl, 3.24 mmol) in methylene chloride (25 ml). The mixture was stirred at ambient temperature for 1 hour and the residue was purified by column chromatography eluting with increasingly polar mixtures of methylene chloride and methanol. The fractions containing the expected product were combined and evaporated. The residue was triturated under diethyl ether and the solid was filtered, washed with diethyl ether and evaporated to give 7-(3-bromopropoxy)-4-(4-fluoro-2-methylindol-5-yloxy)-6-methoxyquinazoline (1.35 g, 100%).

Workup

  1. customthe residue was purified by column chromatography
  2. washeluting
  3. temperaturewith increasingly polar mixtures of methylene chloride and methanol
  4. additionThe fractions containing the expected product
  5. customevaporated
  6. customThe residue was triturated under diethyl ether
  7. filtrationthe solid was filtered
  8. washwashed with diethyl ether
  9. customevaporated

Sources & evidence

ORD record
ord-4852d5c5dd9f4bb6a148b82ac2a9f856
Source dataset
uspto-grants-2007_09
Patent number
US07268230B2

Reaction notes

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