Hydrazine → N-((1S)-2-amino-1-{[2-(trifluoromethyl)phenyl]methyl}ethyl)-5-chloro-4-(4-chloro-1-methyl-1H-pyrazol-5-yl)-2-furancarboxamide

HRID 1845543Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1845543
[Cl:1][C:2]1[O:6][C:5]([C:7]([NH:9][C@@H:10]([CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=2[C:30]([F:33])([F:32])[F:31])[CH2:11][N:12]2C(=O)C3C(=CC=CC=3)C2=O)=[O:8])=[CH:4][C:3]=1[C:34]1[N:38]([CH3:39])[N:37]=[CH:36][C:35]=1[Cl:40].NN>O1CCCC1.CO>[NH2:12][CH2:11][C@@H:10]([NH:9][C:7]([C:5]1[O:6][C:2]([Cl:1])=[C:3]([C:34]2[N:38]([CH3:39])[N:37]=[CH:36][C:35]=2[Cl:40])[CH:4]=1)=[O:8])[CH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=1[C:30]([F:33])([F:32])[F:31]

Komponenten

5

Edukt 2

HCID 9321HydrazineHCID 578266885-chloro-4-(4-chloro-1-methyl-1H-pyrazol-5-yl)-N-((1S)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-1-{[2-(trifluoromethyl)phenyl]methyl}ethyl)-2-furancarboxamide

Produkt 1

HCID 57826499N-((1S)-2-amino-1-{[2-(trifluoromethyl)phenyl]methyl}ethyl)-5-chloro-4-(4-chloro-1-methyl-1H-pyrazol-5-yl)-2-furancarboxamideAusbeute 65 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 887MethanolLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

To a solution of 5-chloro-4-(4-chloro-1-methyl-1H-pyrazol-5-yl)-N-((1S)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-1-{[2-(trifluoromethyl)phenyl]methyl}ethyl)-2-furancarboxamide (116 mg, 0.20 mmol) in tetrahydrofuran (1 ml) and methanol (1 ml) at 25° C. was added hydrazine (0.04 ml, 1.37 mmol) dropwise. After 12 h the solution was concentrated, dry loaded onto silica and purified by column chromatography (2% MeOH in DCM (1% NH4OH)). The free base was transferred to the HCl salt by addition of excess 2M HCl in Ether (2 ml) to the residue in DCM (2 ml) affording the HCl salt of N-((1S)-2-amino-1-{[2-(trifluoromethyl)phenyl]methyl}ethyl)-5-chloro-4-(4-chloro-1-methyl-1H-pyrazol-5-yl)-2-furancarboxamide (68 mg, 0.13 mmol, 65% yield) as a yellow solid: LCMS (ES) m/z=461, 463 (M, M+2)+, 1H NMR (400 MHz, DMSO-d6) δ ppm 8.80 (d, J=9.09 Hz, 1H) 8.03 (br. s., 3H) 7.66-7.73 (m, 2H) 7.58-7.61 (m, 1H) 7.52-7.59 (m, 2H) 7.40-7.48 (m, 1H) 4.5-4.57 (m, 1H) 3.77 (s, 3H) 2.98-3.09 (m, 4H).

Aufarbeitung

  1. concentrationAfter 12 h the solution was concentrated
  2. customdry loaded onto silica
  3. custompurified by column chromatography (2% MeOH in DCM (1% NH4OH))
  4. additionThe free base was transferred to the HCl salt by addition of excess 2M HCl in Ether (2 ml) to the residue in DCM (2 ml)

Quellen und Nachweise

ORD-Eintrag
ord-3bf49ede0a954cb6b9fed249576899c4
Quelldatensatz
uspto-grants-2015_02
Patentnummer
US08946278B2

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