Triphenylphosphine → 6-[2-(4-acetylpiperazin-1-yl)ethoxy]-4-[(4-fluoro-1H-indol-5-yl)oxy]-7-methoxyquinazoline

HRID 916467Notes

Reaction equation

HRID 916467 reaction equation
[F:1][C:2]1[C:10]([O:11][C:12]2[C:21]3[C:16](=[CH:17][C:18]([O:23][CH3:24])=[C:19]([OH:22])[CH:20]=3)[N:15]=[CH:14][N:13]=2)=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[CH:5][NH:6]2.[C:25]([N:28]1[CH2:33][CH2:32][N:31]([CH2:34][CH2:35]O)[CH2:30][CH2:29]1)(=[O:27])[CH3:26].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>ClCCl>[C:25]([N:28]1[CH2:33][CH2:32][N:31]([CH2:34][CH2:35][O:22][C:19]2[CH:20]=[C:21]3[C:16](=[CH:17][C:18]=2[O:23][CH3:24])[N:15]=[CH:14][N:13]=[C:12]3[O:11][C:10]2[C:2]([F:1])=[C:3]3[C:7](=[CH:8][CH:9]=2)[NH:6][CH:5]=[CH:4]3)[CH2:30][CH2:29]1)(=[O:27])[CH3:26]

Participants

6

Reactant 4

HCID 11776Triphenylphosphine2×HCID 75555Diisopropyl diazene-1,2-dicarboxylate2×HCID 47396291-Acetyl-4-(2-hydroxyethyl)piperazine2×HCID 589602194-[(4-fluoro-1H-indol-5-yl)oxy]-6-hydroxy-7-methoxyquinazoline

Product 1

HCID 101279706-[2-(4-acetylpiperazin-1-yl)ethoxy]-4-[(4-fluoro-1H-indol-5-yl)oxy]-7-methoxyquinazolineYield 68%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of 4-[(4-fluoro-1H-indol-5-yl)oxy]-6-hydroxy-7-methoxyquinazoline (260 mg, 0.80 mmol), (prepared as described for the starting material in Example 10), 2-(4-acetylpiperazin-1-yl)ethanol (165 mg, 0.96 mmol), (prepared as described for the starting material in Example 28), and triphenylphosphine (252 mg, 0.96 mmol) in dichloromethane (15 ml) was stirred and cooled in an ice/water bath. Diisopropyl azodicarboxylate (189 μl, 0.96 mmol) was added. The mixture was stirred for 3 hours and then a further 0.5 mole equivalent of 2-(4-acetylpiperazin-1-yl)ethanol, triphenylphosphine and diisopropyl azodicarboxylate were added. The mixture was stirred for a further 1 hour and then concentrated under reduced pressure. The residue was purified by column chromatography eluting with methylene chloride/methanol (95/5) to give 6-[2(4-acetylpiperazin-1-yl)ethoxy]-4-[(4-fluoro-1H-indol-5-yl)oxy]-7-methoxyquinazoline (260 mg, 68%) as a white solid.

Workup

  1. custom(prepared
  2. custom(prepared
  3. temperaturecooled in an ice/water bath
  4. stirringThe mixture was stirred for 3 hours
  5. stirringThe mixture was stirred for a further 1 hour
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by column chromatography
  8. washeluting with methylene chloride/methanol (95/5)

Sources & evidence

ORD record
ord-910dc205e4d44d6cb5a350595cbc5137
Source dataset
uspto-grants-2007_09
Patent number
US07268230B2

Reaction notes

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