Trifluoroacetic acid → HCID 71626161, Verbindung

HRID 1396395Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1396395
[C:1]([C:4]1[N:9]=[N:8][C:7]([NH:10][C@@H:11]2[CH2:16][CH2:15][CH2:14][CH2:13][C@@H:12]2[NH:17]C(=O)OC(C)(C)C)=[CH:6][C:5]=1[NH:25][C:26]1[CH:31]=[C:30]([CH3:32])[CH:29]=[C:28]([CH3:33])[N:27]=1)(=[O:3])[NH2:2].[F:34][C:35]([F:40])([F:39])[C:36]([OH:38])=[O:37]>ClCCl>[F:34][C:35]([F:40])([F:39])[C:36]([OH:38])=[O:37].[NH2:17][C@H:12]1[CH2:13][CH2:14][CH2:15][CH2:16][C@H:11]1[NH:10][C:7]1[N:8]=[N:9][C:4]([C:1]([NH2:2])=[O:3])=[C:5]([NH:25][C:26]2[CH:31]=[C:30]([CH3:32])[CH:29]=[C:28]([CH3:33])[N:27]=2)[CH:6]=1

Komponenten

4

Edukt 2

HCID 6422Trifluoroacetic acidHCID 86689750tert-butyl (1S,2R)-2-(6-carbamoyl-5-(4,6-dimethylpyridin-2-ylamino)pyridazin-3-ylamino)cyclohexylcarbamate

Produkt 1

HCID 71626161HCID 71626161, VerbindungAusbeute 43 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

To a solution of tert-butyl (1S,2R)-2-(6-carbamoyl-5-(4,6-dimethylpyridin-2-ylamino)pyridazin-3-ylamino)cyclohexylcarbamate (75 mg, 165 μmol) in dichloromethane (5 mL) was added trifluoroacetic acid (1.88 g, 1.27 mL, 16.5 mmol) and the mixture stirred at room temperature for 16 h. The mixture was concentrated and then the residue was diluted with dichloromethane and neutralized with NH4OH. Purification by chromatography (silica, 0-100% of a 10:0.5:89.5 methanol:NH4OH:dichloromethane in dichloromethane) followed by further purification by HPLC (C-18, 10-100% water in acetonitrile gradient) gave 6-((1R,2S)-2-aminocyclohexylamino)-4-(4,6-dimethylpyridin-2-ylamino)pyridazine-3-carboxamide 2,2,2-trifluoroacetate (33 mg, 70.3 μmol, 43%) as a fluffy off white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 11.66 (s, 1H), 8.38 (s, 1H), 8.25 (s, 1H), 7.86 (br. s, 1H), 7.40 (br. s, 2H), 6.76 (s, 1H), 6.65 (s, 1H), 4.40 (s., 1H), 3.63 (s, 1H), 2.48 (s, 3H), 1.58-1.86 (m, 8H), 1.46 (m, 2H); MS (EI/CI) m/z: 356.1 [M+H].

Aufarbeitung

  1. concentrationThe mixture was concentrated
  2. additionthe residue was diluted with dichloromethane and neutralized with NH4OH
  3. customPurification by chromatography (silica, 0-100% of a 10:0.5:89.5 methanol:NH4OH:dichloromethane in dichloromethane)
  4. customfollowed by further purification by HPLC (C-18, 10-100% water in acetonitrile gradient)

Quellen und Nachweise

ORD-Eintrag
ord-58eadd1a0b064a48bcccdf246ffd870e
Quelldatensatz
uspto-grants-2014_12
Patentnummer
US08901124B2

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