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

반응식

HRID 1943460 반응식
[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]

참가 물질

9

반응물 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

생성물 1

HCID 596246128-(6-acetamido-4-chloropyridin-2-ylamino)-6-chloro-N-(3-fluoropyridin-4-yl)imidazo[1,2-b]pyridazine-3-carboxamide수율 68.4%

시약·촉매·용매 3

HCID 81531Diisopropylethylamine촉매HCID 6228Dimethylformamide용매HCID 8028Tetrahydrofuran용매

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-165dcce456f54738aca5fe8e8331f26c
출처 데이터셋
uspto-grants-2013_03
특허 번호
US08389527B2

연결된 노트

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