Ammonium formate → Azd-7624

HRID 869818Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 869818
Br[C:2]1[N:7]=[C:6]([NH:8][C:9]2([C:12]3[CH:32]=[CH:31][CH:30]=[CH:29][C:13]=3[O:14][CH2:15][CH2:16][N:17](C)[C:18](=O)OCC3C=CC=CC=3)[CH2:11][CH2:10]2)[C:5](=[O:33])[N:4]([C:34]2[CH:39]=[C:38]([C:40](=[O:45])[NH:41][CH:42]3[CH2:44][CH2:43]3)[CH:37]=[C:36]([F:46])[C:35]=2[CH3:47])[CH:3]=1.C([O-])=O.[NH4+]>C(O)(C)C.[Pd]>[CH:42]1([NH:41][C:40](=[O:45])[C:38]2[CH:39]=[C:34]([N:4]3[CH:3]=[CH:2][N:7]=[C:6]([NH:8][C:9]4([C:12]5[CH:32]=[CH:31][CH:30]=[CH:29][C:13]=5[O:14][CH2:15][CH2:16][NH:17][CH3:18])[CH2:11][CH2:10]4)[C:5]3=[O:33])[C:35]([CH3:47])=[C:36]([F:46])[CH:37]=2)[CH2:44][CH2:43]1

Komponenten

5

Edukt 2

HCID 2723923Ammonium formateHCID 58072137Benzyl[2-[2-[1-[[6-bromo-4-[5-(cyclopropylcarbamoyl)-3-fluoro-2-methylphenyl]-3-oxo-3,4-dihydro-2-pyrazinyl]amino]cyclopropyl]phenoxy]ethyl]methylcarbamate

Produkt 1

HCID 25143624Azd-7624Ausbeute 81,9 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 23938PalladiumKatalysatorHCID 3776IsopropanolLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

10% Pd/C (87 L paste ex. Johnson Matthey, 110 mg) was washed with isopropanol (10 mL) and then suspended in further isopropanol (10 mL). A sample of this suspension (291 μL, ˜3.2 mg Pd/C) was added to a solution of benzyl [2-[2-[1-[[6-bromo-4-[5-(cyclopropylcarbamoyl)-3-fluoro-2-methylphenyl]-3-oxo-3,4-dihydro-2-pyrazinyl]amino]cyclopropyl]phenoxy]ethyl]methylcarbamate (Preparation 4e, 10.5 mg, 14.9 μmol) and ammonium formate (33.3 mg, 512 μmol) in isopropanol (0.1 mL). The reaction vessel was sealed and the suspension heated to 80° C. (jacket temperature) for 10 min. The reaction mixture was then filtered through Celite and the cake washed with ethyl acetate. The filtrates were combined and washed with brine that had been basified to pH 12 with KOH. The solution was filtered through a short pad of sodium sulfate and concentrated to dryness in vacuo to afford N-cyclopropyl-3-fluoro-4-methyl-5-[3-[1-[2-[2-(methylamino)ethoxy]phenyl]cyclopropylamino]-2-oxo-1(2H)-pyrazinyl]benzamide (6.0 mg) as a colourless solid.

Aufarbeitung

  1. wash10% Pd/C (87 L paste ex. Johnson Matthey, 110 mg) was washed with isopropanol (10 mL)
  2. customThe reaction vessel was sealed
  3. filtrationThe reaction mixture was then filtered through Celite
  4. washthe cake washed with ethyl acetate
  5. washwashed with brine that
  6. filtrationThe solution was filtered through a short pad of sodium sulfate
  7. concentrationconcentrated to dryness in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-d0f6ee08ed4b4a3f9ee292e5631e059b
Quelldatensatz
uspto-grants-2015_03
Patentnummer
US08969350B2

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