Aluminum(III) Chloride → [4-Amino-2-(1-methanesulfonyl-piperidin-4-ylamino)-pyrimidin-5-yl]-(2,3-difluoro-6-hydroxy-5-methoxy-phenyl)-methanone

HRID 1371726ノート

反応式

HRID 1371726 の反応式
[NH2:1][C:2]1[C:7]([C:8]([C:10]2[C:15]([O:16]C)=[C:14]([O:18][CH3:19])[CH:13]=[C:12]([F:20])[C:11]=2[F:21])=[O:9])=[CH:6][N:5]=[C:4]([NH:22][CH:23]2[CH2:28][CH2:27][N:26]([S:29]([CH3:32])(=[O:31])=[O:30])[CH2:25][CH2:24]2)[N:3]=1.[Cl-].[Al+3].[Cl-].[Cl-]>C(Cl)Cl>[NH2:1][C:2]1[C:7]([C:8]([C:10]2[C:15]([OH:16])=[C:14]([O:18][CH3:19])[CH:13]=[C:12]([F:20])[C:11]=2[F:21])=[O:9])=[CH:6][N:5]=[C:4]([NH:22][CH:23]2[CH2:24][CH2:25][N:26]([S:29]([CH3:32])(=[O:30])=[O:31])[CH2:27][CH2:28]2)[N:3]=1

参加物

4

反応物 2

HCID 6451240Aluminum(III) ChlorideHCID 58777551HCID 58777551、化合物

生成物 1

HCID 58777669[4-Amino-2-(1-methanesulfonyl-piperidin-4-ylamino)-pyrimidin-5-yl]-(2,3-difluoro-6-hydroxy-5-methoxy-phenyl)-methanone収率 52%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

To a solution of [4-amino-2-(1-methanesulfonyl-piperidin-4-ylamino)-pyrimidin-5-yl]-(2,3-difluoro-5,6-dimethoxy-phenyl)-methanone (30 mg, 0.0636 mmol, Example 261) in methylene chloride (20 mL) cooled to 5° C. was added aluminum chloride (129 mg, 0.954 mmol, Fluka). The reaction mixture was stirred at room temperature for 24 hours and quenched with water. Tetrahydrofuran (40 mL) was added and the layers were separated. The organic layer was washed with water (1×5 mL), brine (1×5 mL) and dried over anhydrous sodium sulfate. The solids were filtered off and the filtrate was concentrated in vacuo. Purification of the crude residue by flash chromatography (Biotage system, 60 Å silica gel, eluting with ethyl acetate) yielded [4-amino-2-(1-methanesulfonyl-piperidin-4-ylamino)-pyrimidin-5-yl]-(2,3-difluoro-6-hydroxy-5-methoxy-phenyl)-methanone as yellow solids (15 mg, 52%). HR-MS (ES, m/z) calculated for C18H22N5O5SF2 [(M+H)+] 458.1307, observed 458.1304.

後処理

  1. customquenched with water
  2. additionTetrahydrofuran (40 mL) was added
  3. customthe layers were separated
  4. washThe organic layer was washed with water (1×5 mL), brine (1×5 mL)
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationThe solids were filtered off
  7. concentrationthe filtrate was concentrated in vacuo
  8. customPurification of the crude residue
  9. washby flash chromatography (Biotage system, 60 Å silica gel, eluting with ethyl acetate)

出典と根拠

ORDレコード
ord-a4539a844fe644f28e56338990c965b7
出典データセット
uspto-grants-2007_01
特許番号
US07157455B2

反応ノート

読み込み中…