Triphenylphosphine → 6-(3-Bromopropoxy)-4-(4-fluoro-2-methylindol-5-yloxy)-7-methoxyquinazoline

HRID 916410Notes

Reaction equation

HRID 916410 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]([O:35][CH3:36])=[C:31]([OH:34])[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.CCOC(/N=N/C(OCC)=O)=O>C(Cl)Cl>[Br:57][CH2:58][CH2:59][CH2:60][O:34][C:31]1[CH:32]=[C:33]2[C:28](=[CH:29][C:30]=1[O:35][CH3:36])[N:27]=[CH:26][N:25]=[C:24]2[O:23][C:22]1[C:14]([F:13])=[C:15]2[C:19](=[CH:20][CH:21]=1)[NH:18][C:17]([CH3:37])=[CH:16]2

Participants

7

Reactant 5

HCID 11776Triphenylphosphine2×HCID 123083-Bromo-1-propanolHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 5462977Diethyl azodicarboxylateHCID 112677704-(4-Fluoro-2-methylindol-5-yloxy)-6-hydroxy-7-methoxyquinazoline

Product 1

HCID 589602506-(3-Bromopropoxy)-4-(4-fluoro-2-methylindol-5-yloxy)-7-methoxyquinazolineYield 73.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Diethyl azodicarboxylate (0.847 g, 4.86 mmol) was added to a solution of 4-(4-fluoro-2-methylindol-5-yloxy)-6-hydroxy-7-methoxyquinazoline (1.5 g, 4.42 mmol), (prepared as described for the starting material in Example 1), triphenylphosphine (1.74 g, 6.63 mmol) and 3-bromo-1-propanol (0.923 g, 6.63 mol) in methylene chloride. After stirring for 1 hour at ambient temperature, triphenylphosphine (1.16 g) and DEAD (0.770 g) was added. After stirring for 30 minutes, the volatiles were removed under vacuum and the residue was purified by column chromatography eluting with increasingly polar mixtures of methylene chloride and ethyl acetate to give 6-(3-bromopropoxy)-4-(4-fluoro-2-methylindol-5-yloxy)-7-methoxyquinazoline (1.5 g, 73%).

Workup

  1. custom(prepared
  2. stirringAfter stirring for 30 minutes
  3. customthe volatiles were removed under vacuum
  4. customthe residue was purified by column chromatography
  5. washeluting
  6. temperaturewith increasingly polar mixtures of methylene chloride and ethyl acetate

Sources & evidence

ORD record
ord-7877a5801a174aa1ae5c352d947d5e33
Source dataset
uspto-grants-2007_09
Patent number
US07268230B2

Reaction notes

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