Trifluoroacetic acid → HCID 49764272、化合物

HRID 1256244ノート

反応式

HRID 1256244 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]([CH:19]=[O:20])[CH:15]=[CH:14][C:13]=2[C:12]2[N:21](COCC[Si](C)(C)C)[N:22]=[C:23]([NH:24][CH:25]3[CH2:30][CH2:29][N:28]([S:31]([CH3:34])(=[O:33])=[O:32])[CH2:27][CH2:26]3)[C:11]=2[N:10]=1.C(O)(C(F)(F)F)=O>C(Cl)Cl.C([O-])(O)=O.[Na+]>[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]([CH:19]=[O:20])[CH:15]=[CH:14][C:13]=2[C:12]2[NH:21][N:22]=[C:23]([NH:24][CH:25]3[CH2:30][CH2:29][N:28]([S:31]([CH3:34])(=[O:32])=[O:33])[CH2:27][CH2:26]3)[C:11]=2[N:10]=1

参加物

5

反応物 2

HCID 6422Trifluoroacetic acidHCID 86664925HCID 86664925、化合物

生成物 1

HCID 49764272HCID 49764272、化合物

試薬・触媒・溶媒 2

HCID 6344Dichloromethane溶媒HCID 516892Sodium Bicarbonate溶媒

反応条件

温度
0 °C

実験手順

A 10 ml round-bottomed flask is charged with 54 mg of 5-(2,6-difluorophenyl)-3-{[1-(methylsulphonyl)piperidin-4-yl]amino}-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrazolo[4,3-c]isoquinoline-7-carbaldehyde, prepared in step 5 of example 2, in 5 ml of DCM. After cooling to 0° C. using an ice bath, 0.3 ml of TFA is added and the mixture is stirred at RT for 16 h. It is concentrated under RP and the solid obtained is taken up in 5 ml of saturated aqueous NaHCO3 solution. It is extracted with AcOEt, dried over MgSO4, filtered and concentrated under RP. The product is purified by flash chromatography on silica gel (15-40 μm), eluting with a mixture of DCM/AcOEt (50/50 by vol.). This gives 9 mg of 5-(2,6-difluorophenyl)-3-{[1-(methylsulphonyl)piperidin-4-yl]amino}-1H-pyrazolo[4,3-c]isoquinoline-7-carbaldehyde (yellow solid). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.68 (m, 2 H) 2.11 (m, 2 H) 2.88 (s, 3 H) 2.90 (m, 2 H) 3.57 (m, 2 H) 3.81 (m, 1 H) 6.16 (broad m, 1 H) 7.36 (t, J=7.8 Hz, 2 H) 7.71 (m, 1 H) 8.23 (broad s, 1 H) 8.34 (broad d, J=8.5 Hz, 1 H) 8.57 (d, J=8.2 Hz, 1 H) 10.10 (s, 1 H) 13.02 (broad s, 1 H). LC-MS-DAD-ELSD: 486 (+)=(M+H)(+).

後処理

  1. concentrationIt is concentrated under RP
  2. customthe solid obtained
  3. extractionIt is extracted with AcOEt
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated under RP
  7. customThe product is purified by flash chromatography on silica gel (15-40 μm)
  8. washeluting with a mixture of DCM/AcOEt (50/50 by vol.)

出典と根拠

ORDレコード
ord-ec23f3bb911340bd84e193bf0efd923e
出典データセット
uspto-grants-2013_06
特許番号
US08461175B2

反応ノート

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