Triphenylphosphine → 6-(3-(4-Acetylpiperazin-1-yl)propoxy)-4-(4-fluoro-2-methylindol-5-yloxy)-7-methoxyquinazoline

HRID 2068012노트

반응식

HRID 2068012 반응식
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.[C:57]([N:60]1[CH2:65][CH2:64][N:63]([CH2:66][CH2:67][CH2:68]O)[CH2:62][CH2:61]1)(=[O:59])[CH3:58]>C(Cl)Cl>[C:57]([N:60]1[CH2:65][CH2:64][N:63]([CH2:66][CH2:67][CH2:68][O:34][C:31]2[CH:32]=[C:33]3[C:28](=[CH:29][C:30]=2[O:35][CH3:36])[N:27]=[CH:26][N:25]=[C:24]3[O:23][C:22]2[C:14]([F:13])=[C:15]3[C:19](=[CH:20][CH:21]=2)[NH:18][C:17]([CH3:37])=[CH:16]3)[CH2:62][CH2:61]1)(=[O:59])[CH3:58]

참가 물질

6

반응물 4

HCID 11776Triphenylphosphine2회HCID 220568ethyl N-ethoxycarbonyliminocarbamate2회HCID 112677704-(4-Fluoro-2-methylindol-5-yloxy)-6-hydroxy-7-methoxyquinazolineHCID 114467711-(4-(3-Hydroxypropyl)piperazin-1-yl)ethan-1-one

생성물 1

HCID 101745406-(3-(4-Acetylpiperazin-1-yl)propoxy)-4-(4-fluoro-2-methylindol-5-yloxy)-7-methoxyquinazoline수율 60%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

Diethyl azodicarboxylate (0.178 g, 1.02 mmol) was added to a solution of 4-(4-fluoro-2-methylindol-5-yloxy)-6-hydroxy-7-methoxyquinazoline (0.267 g, 0.787 mmol), triphenylphosphine (0.31 g, 1.18 mmol) and 3-(4-acetylpiperazin-1-yl)propan-1-ol (0.176 g, 0.945 mmol) in methylene chloride (10 nm). After stirring for 15 minutes at ambient temperature, further triphenylphosphine (0.062 mg, 0.236 mmol) and diethyl azodicarboxylate (0.041 mg, 0.3 mmol) were added. After stirring for 1 hour at ambient temperature, the mixture was poured onto a column of silica and eluted with increasingly polar mixtures of ethyl acetate and methylene chloride followed by 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 ether and dried under vacuum to give 6-(3-(4-acetylpiperazin-1-yl)propoxy)-4-(4-fluoro-2-methylindol-5-yloxy)-7-methoxyquinazoline 0.210 g, 60%).

후처리

  1. stirringAfter stirring for 1 hour at ambient temperature
  2. additionthe mixture was poured onto a column of silica
  3. washeluted
  4. temperaturewith increasingly polar mixtures of ethyl acetate and methylene chloride
  5. additionThe fractions containing the expected product
  6. customevaporated
  7. customThe residue was triturated under diethyl ether
  8. filtrationthe solid was filtered
  9. washwashed with ether
  10. customdried under vacuum

출처 및 근거

ORD 기록
ord-b80d09c077a240cfac3062bd8df4ab6c
출처 데이터셋
uspto-grants-2012_10
특허 번호
US08293902B2

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