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

HRID 916467노트

반응식

HRID 916467 반응식
[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]

참가 물질

6

반응물 4

HCID 11776Triphenylphosphine2회HCID 75555Diisopropyl diazene-1,2-dicarboxylate2회HCID 47396291-Acetyl-4-(2-hydroxyethyl)piperazine2회HCID 589602194-[(4-fluoro-1H-indol-5-yl)oxy]-6-hydroxy-7-methoxyquinazoline

생성물 1

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

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-910dc205e4d44d6cb5a350595cbc5137
출처 데이터셋
uspto-grants-2007_09
특허 번호
US07268230B2

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