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Trifluoroacetic acid → 5-(2,6-difluorophenyl)-3-{[1-(trifluoromethanesulphonyl)piperidin-4-yl]amino}-1H-pyrazolo[4,3-c]isoquinoline-7-carboxamide

HRID 1256223
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HRID 1256223 반응식
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[C:9]1[C:18]2[CH:17]=[C:16]([C:19]([NH2:21])=[O:20])[CH:15]=[CH:14][C:13]=2[C:12]2[N:22](COCC[Si](C)(C)C)[N:23]=[C:24]([NH:25][CH:26]3[CH2:31][CH2:30][N:29]([S:32]([C:35]([F:38])([F:37])[F:36])(=[O:34])=[O:33])[CH2:28][CH2:27]3)[C:11]=2[N:10]=1.C(O)(C(F)(F)F)=O>C(Cl)Cl.O.N>[F:8][C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[C:3]=1[C:9]1[C:18]2[CH:17]=[C:16]([C:19]([NH2:21])=[O:20])[CH:15]=[CH:14][C:13]=2[C:12]2[NH:22][N:23]=[C:24]([NH:25][CH:26]3[CH2:27][CH2:28][N:29]([S:32]([C:35]([F:38])([F:37])[F:36])(=[O:34])=[O:33])[CH2:30][CH2:31]3)[C:11]=2[N:10]=1
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참가 물질

6

반응물 2

HCID 6422Trifluoroacetic acidHCID 667746395-(2,6-difluorophenyl)-3-{[1-(trifluoromethanesulphonyl)piperidin-4-yl]amino}-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrazolo[4,3-c]isoquinoline-7-carboxamide

생성물 1

HCID 497640125-(2,6-difluorophenyl)-3-{[1-(trifluoromethanesulphonyl)piperidin-4-yl]amino}-1H-pyrazolo[4,3-c]isoquinoline-7-carboxamide수율 12.3%

시약·촉매·용매 3

HCID 222Ammonia
용매
HCID 962Water용매
HCID 6344Dichloromethane용매

실험 절차

A 50 ml round-bottom flask equipped with a magnetic stirrer and with a septum having a top-mounted argon intake is charged with 300 mg of 5-(2,6-difluorophenyl)-3-{[1-(trifluoromethanesulphonyl)piperidin-4-yl]amino}-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrazolo[4,3-c]isoquinoline-7-carboxamide in 8 ml of DCM. 3 ml of TFA are added and the mixture is stirred at RT for 2 h. It is concentrated under RP and the solid obtained is taken up in 30 ml of water and 2 ml of 0.75M aqueous ammonia solution. The product is extracted with AcOEt, dried over MgSO4, filtered and concentrated under RP. Chromatography on silica gel (15-40 μm), eluting with AcOEt, gives 30 mg of 5-(2,6-difluorophenyl)-3-{[1-(trifluoromethanesulphonyl)piperidin-4-yl]amino}-1H-pyrazolo[4,3-c]isoquinoline-7-carboxamide (pale yellow solid). MS (E/I): m/z=554 (M+); 1H NMR: 1.69 (m, 2H); 2.17 (m, 2H); 3.38 (m, 2H); 3.83 (m, 2H); 3.93 (m, 1H); 6.24 (m, 1H); 7.33 (t, J=8.0 Hz, 2H); 7.58 (broad s, 1H); 7.69 (m, 1H); 8.17 (broad s, 1H); 8.23 (broad s, 1H); 8.36 (broad d, J=8.5 Hz, 1H); 8.44 (d, J=8.5 Hz, 1H); 12.9 (broad s, 1H).

후처리

  1. customA 50 ml round-bottom flask equipped with a magnetic stirrer and with a septum
  2. concentrationIt is concentrated under RP
  3. customthe solid obtained
  4. extractionThe product is extracted with AcOEt
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated under RP
  8. washChromatography on silica gel (15-40 μm), eluting with AcOEt

출처 및 근거

ORD 기록
ord-6373cdd0f5844637a8532711883bd2dc
출처 데이터셋
uspto-grants-2013_06
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08461175B2

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