Acetyl chloride → 8-(6-acetamido-4-chloropyridin-2-ylamino)-6-chloro-N-(3-fluoropyridin-4-yl)imidazo[1,2-b]pyridazine-3-carboxamide

HRID 1943460

Reaktionsgleichung

Reaktionsgleichung von HRID 1943460
[Cl:1][C:2]1[CH:7]=[C:6]([NH2:8])[N:5]=[C:4]([NH2:9])[CH:3]=1.[H-].[Na+].Br[C:13]1[C:14]2[N:15]([C:20]([C:23]([NH:25][C:26]3[CH:31]=[CH:30][N:29]=[CH:28][C:27]=3[F:32])=[O:24])=[CH:21][N:22]=2)[N:16]=[C:17]([Cl:19])[CH:18]=1.[C:33](Cl)(=[O:35])[CH3:34].[NH4+].[Cl-]>C1COCC1.CCN(C(C)C)C(C)C.CN(C=O)C>[C:33]([NH:8][C:6]1[N:5]=[C:4]([NH:9][C:13]2[C:14]3[N:15]([C:20]([C:23]([NH:25][C:26]4[CH:31]=[CH:30][N:29]=[CH:28][C:27]=4[F:32])=[O:24])=[CH:21][N:22]=3)[N:16]=[C:17]([Cl:19])[CH:18]=2)[CH:3]=[C:2]([Cl:1])[CH:7]=1)(=[O:35])[CH3:34]

Komponenten

9

Edukt 5

HCID 6367Acetyl chlorideHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 2378474-Chloropyridine-2,6-diamineHCID 596244958-Bromo-6-chloro-N-(3-fluoropyridin-4-yl)imidazo[1,2-b]pyridazine-3-carboxamide

Produkt 1

HCID 596246128-(6-acetamido-4-chloropyridin-2-ylamino)-6-chloro-N-(3-fluoropyridin-4-yl)imidazo[1,2-b]pyridazine-3-carboxamideAusbeute 68,4 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 81531DiisopropylethylamineKatalysatorHCID 6228DimethylformamideLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

To a solution of 4-chloropyridine-2,6-diamine (35.2 mg, 0.245 mmol) in THF (0.5 mL) was added 60% NaH (12.26 mg, 0.307 mmol). The mixture was stirred for 10 min. 5A (40 mg, 0.123 mmol) was added, followed by DMF (0.5 mL). The mixture was stirred at room temperature overnight. To the reaction mixture was added acetyl chloride (0.052 mL, 0.736 mmol) and a few drops of DIEA. The mixture was stirred at 65° C. for 20 min and then cooled to room temperature. Saturated NH4Cl was added and the resulting precipitate was collected by filtration, washed with water, and dried in vacuum to give crude 41A as a yellow solid (40 mg, 49%). HPLC Rt=3.283 min. (Chromolith SpeedROD 4.6×50 mm, 10-90% aqueous methanol containing 0.1% TFA, 4 min gradient, monitored at 220 nm), [M+H]=475.

Aufarbeitung

  1. stirringThe mixture was stirred at room temperature overnight
  2. stirringThe mixture was stirred at 65° C. for 20 min
  3. filtrationthe resulting precipitate was collected by filtration
  4. washwashed with water
  5. customdried in vacuum

Quellen und Nachweise

ORD-Eintrag
ord-165dcce456f54738aca5fe8e8331f26c
Quelldatensatz
uspto-grants-2013_03
Patentnummer
US08389527B2

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