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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
ノート
印刷プレビュー

反応式

HRID 1256223 の反応式
[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
参加物実験手順後処理出典と根拠反応ノート

参加物

6

反応物 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

生成物 1

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

試薬・触媒・溶媒 3

HCID 222Ammonia
溶媒
HCID 962Water溶媒
HCID 6344Dichloromethane溶媒

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-6373cdd0f5844637a8532711883bd2dc
出典データセット
uspto-grants-2013_06
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08461175B2

反応ノート

読み込み中…

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