Regorafenib → 4-[4-({[4-chloro-3-(trifluoromethyl)phenyl]carbamoyl}amino)-3-fluorophenoxy]-N-methylpyridine-2-carboxamide hydrochloride

HRID 475441ノート

反応式

HRID 475441 の反応式
[CH3:1][NH:2][C:3]([C:5]1[CH:10]=[C:9]([O:11][C:12]2[CH:17]=[CH:16][C:15]([NH:18][C:19]([NH:21][C:22]3[CH:27]=[CH:26][C:25]([Cl:28])=[C:24]([C:29]([F:32])([F:31])[F:30])[CH:23]=3)=[O:20])=[C:14]([F:33])[CH:13]=2)[CH:8]=[CH:7][N:6]=1)=[O:4].Cl.O1CCOCC1>O1CCCC1>[ClH:28].[CH3:1][NH:2][C:3]([C:5]1[CH:10]=[C:9]([O:11][C:12]2[CH:17]=[CH:16][C:15]([NH:18][C:19]([NH:21][C:22]3[CH:27]=[CH:26][C:25]([Cl:28])=[C:24]([C:29]([F:32])([F:31])[F:30])[CH:23]=3)=[O:20])=[C:14]([F:33])[CH:13]=2)[CH:8]=[CH:7][N:6]=1)=[O:4]

参加物

4

反応物 2

HCID 11167602RegorafenibHCID 204431481,4-Dioxane hydrochloride

生成物 1

HCID 665770094-[4-({[4-chloro-3-(trifluoromethyl)phenyl]carbamoyl}amino)-3-fluorophenoxy]-N-methylpyridine-2-carboxamide hydrochloride

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

The compound of example 1 as a free base (2.0 g) was dissolved in anhydrous tetrahydrofuran (15 mL) and a 4M HCl/dioxane was added (excess). The solution was then concentrated in vacuo to afford 2.32 grams of off-white solids. The crude salt was dissolved in hot ethanol (125 mL), activated carbon was added and the mixture heated at reflux for 15 minutes. The hot suspension was filtered through a pad of Celite 521 and allowed to cool to room temperature. The flask was placed in a freezer overnight. The crystalline solids were collected by suction filtration, washed with ethanol, then hexane and air-dried. The mother liquors were concentrated down and crystallization (in freezer) allowed taking place overnight. A second crop of solids was collected and combined with the first crop. The colorless salt was dried in a vacuum oven at 60° C. over two days. Yield of hydrochloride salt obtained 1.72 g (79%).

後処理

  1. concentrationThe solution was then concentrated in vacuo

出典と根拠

ORDレコード
ord-b8048c0d2b2040b7820577b293d6f300
出典データセット
uspto-grants-2014_01
特許番号
US08637553B2

反応ノート

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