Trifluoroacetic acid → HCID 49764272, Verbindung

HRID 1256244Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1256244
[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

Komponenten

5

Edukt 2

HCID 6422Trifluoroacetic acidHCID 86664925HCID 86664925, Verbindung

Produkt 1

HCID 49764272HCID 49764272, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6344DichloromethaneLösungsmittelHCID 516892Sodium BicarbonateLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

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)(+).

Aufarbeitung

  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.)

Quellen und Nachweise

ORD-Eintrag
ord-ec23f3bb911340bd84e193bf0efd923e
Quelldatensatz
uspto-grants-2013_06
Patentnummer
US08461175B2

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