Cyanogen Bromide → [6-(5-Amino-[1,3,4]oxadiazol-2-yl)-4-fluoro-1H-benzoimidazol-5-yl]-(4-bromo-2-methyl-phenyl)-amine

HRID 216464

反応式

HRID 216464 の反応式
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[C:10]([C:19]([NH:21][NH2:22])=[O:20])=[CH:11][C:12]3[NH:16][CH:15]=[N:14][C:13]=3[C:17]=2[F:18])=[C:4]([CH3:23])[CH:3]=1.[N:24]#[C:25]Br.C([O-])(O)=O.[Na+]>O1CCOCC1.C(Cl)Cl.O.[Cl-].[Na+].O>[NH2:24][C:25]1[O:20][C:19]([C:10]2[C:9]([NH:8][C:5]3[CH:6]=[CH:7][C:2]([Br:1])=[CH:3][C:4]=3[CH3:23])=[C:17]([F:18])[C:13]3[N:14]=[CH:15][NH:16][C:12]=3[CH:11]=2)=[N:21][N:22]=1

参加物

8

反応物 3

HCID 10476Cyanogen BromideHCID 516892Sodium BicarbonateHCID 668979206-(4-Bromo-2-methyl-phenylamino)-7-fluoro-3H-benzoimidazole-5-carboxylic acid hydrazide

生成物 1

HCID 10150820[6-(5-Amino-[1,3,4]oxadiazol-2-yl)-4-fluoro-1H-benzoimidazol-5-yl]-(4-bromo-2-methyl-phenyl)-amine収率 55%

試薬・触媒・溶媒 4

HCID 962Water溶媒2 回HCID 6344Dichloromethane溶媒HCID 312751,4-Dioxane溶媒HCID 57417360Sodium chloride; water溶媒

実験手順

6-(4-Bromo-2-methyl-phenylamino)-7-fluoro-3H-benzoimidazole-5-carboxylic acid hydrazide 20a (0.041 g, 0.109 mmol) is suspended in 1,4-dioxane (1.5 mL) and 36 μL of a 3 M solution of cyanogen bromide in methylene chloride is added. NaHCO3 (9 mg, 0.109 mmol) in water (1.5 mL) is then added. After 16 hours, the reaction mixture is diluted with water and brine and extracted with THF. The combined organic extracts are dried (Na2SO4) and concentrated under reduced pressure. Purification by FCC eluted with 98:2 ethyl acetate:MeOH provides 24 mg (55%) of pure desired product as a yellow solid: LC/MS ESI (+) m/z 403, 405 (M+ Br pattern) detected; 1H-NMR (400 MHz, DMSO-d6) δ 12.97 (s, 1H), 8.42 (s, 1H), 7.94 (s, 1H), 7.74 (s, 1H), 7.36 (s, 2H), 7.33 (d, 1H), 7.15 (d, 1H), 6.40 (bs, 1H), 2.34 (s, 3H).

後処理

  1. extractionextracted with THF
  2. dry with materialThe combined organic extracts are dried (Na2SO4)
  3. concentrationconcentrated under reduced pressure
  4. customPurification by FCC
  5. washeluted with 98:2 ethyl acetate

出典と根拠

ORDレコード
ord-dd3f76d0868d4f71979d523dde748410
出典データセット
uspto-grants-2012_06
特許番号
US08193229B2

関連ノート

読み込み中…