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

反応式

HRID 1943460 の反応式
[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]

参加物

9

反応物 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

生成物 1

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

試薬・触媒・溶媒 3

HCID 81531Diisopropylethylamine触媒HCID 6228Dimethylformamide溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-165dcce456f54738aca5fe8e8331f26c
出典データセット
uspto-grants-2013_03
特許番号
US08389527B2

関連ノート

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