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Triphenylphosphine → 4-(4-Fluoro-2-methylindol-5-yl)oxy-6-methoxy-7-(3-(4-methylsulfonylpiperazin-1-yl)propoxy)cinnoline

HRID 2180148
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HRID 2180148 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]([OH:36])=[C:31]([O:34][CH3:35])[CH:32]=3)[N:27]=[N:26][CH: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.[CH3:57][S:58]([N:61]1[CH2:66][CH2:65][N:64]([CH2:67][CH2:68][CH2:69]O)[CH2:63][CH2:62]1)(=[O:60])=[O:59]>CN(C=O)C.C(Cl)Cl>[F:13][C:14]1[C:22]([O:23][C:24]2[C:33]3[C:28](=[CH:29][C:30]([O:36][CH2:69][CH2:68][CH2:67][N:64]4[CH2:65][CH2:66][N:61]([S:58]([CH3:57])(=[O:60])=[O:59])[CH2:62][CH2:63]4)=[C:31]([O:34][CH3:35])[CH:32]=3)[N:27]=[N:26][CH:25]=2)=[CH:21][CH:20]=[C:19]2[C:15]=1[CH:16]=[C:17]([CH3:37])[NH:18]2
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참가 물질

7

반응물 4

HCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 219360993-(4-Methylsulfonylpiperazin-1-yl)propan-1-olHCID 1357497764-(4-Fluoro-2-methylindol-5-yloxy)-7-hydroxy-6-methoxycinnoline

생성물 1

HCID 224900254-(4-Fluoro-2-methylindol-5-yl)oxy-6-methoxy-7-(3-(4-methylsulfonylpiperazin-1-yl)propoxy)cinnoline수율 28%

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 6344Dichloromethane용매

실험 절차

Under nitrogen, diethyl azodicarboxylate (0.19 ml, 1.2 mmol) was added dropwise to a suspension of 4-(4-fluoro-2-methylindol-5-yloxy)-7-hydroxy-6-methoxycinnoline (0.2 g, 0.6 mmol), (prepared as described in Example 4), triphenylphosphine (0.31 g, 1.2 mmol) and 3-(4-methylsulfonylpiperazin-1-yl)propan-1-ol (0.2 g, 0.9 mmol) in DMF (4 ml). The mixture was stirred for 2 hours at ambient temperature. Methylene chloride was added and the mixture was poured onto silica and eluted with ethyl acetate/methylene chloride (1/1) followed by methanol/ethyl acetate/methylene chloride (1/4/4) followed by methanol/methylene chloride (1/9). The fractions containing the expected product were combined and evaporated. The residue was triturated with diethyl ether and filtered. The solid was washed with ether and dried under vacuum to give 4-(4-fluoro-2-methylindol-5-yl)oxy-6-methoxy-7-(3-(4-methylsulfonylpiperazin-1-yl)propoxy)cinnoline (90 mg, 28%).

후처리

  1. additionthe mixture was poured onto silica
  2. washeluted with ethyl acetate/methylene chloride (1/1)
  3. additionThe fractions containing the expected product
  4. customevaporated
  5. customThe residue was triturated with diethyl ether
  6. filtrationfiltered
  7. washThe solid was washed with ether
  8. customdried under vacuum

출처 및 근거

ORD 기록
ord-61ac0c772bec4aea8ff3b760f0c23612
출처 데이터셋
uspto-grants-2005_05
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US06887874B2

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