Hydrochloric Acid → 2-[2-(3-Chloro-benzyl)-5-fluoro-benzoimidazol-1-yl]-2,N-dicyclohexyl-acetamide

HRID 1678811ノート

反応式

HRID 1678811 の反応式
C(O[C:6](=O)[NH:7][C:8]1[CH:13]=[C:12]([F:14])[CH:11]=[CH:10][C:9]=1[NH2:15])(C)(C)C.[CH:17]1([CH:23]=O)[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]1.Cl[C:26]1[CH:27]=[C:28]([CH2:32][C:33]([OH:35])=O)[CH:29]=[CH:30][CH:31]=1.[CH:36]1([N+:42]#[C-])[CH2:41][CH2:40][CH2:39][CH2:38][CH2:37]1.[ClH:44]>CO.O1CCOCC1>[Cl:44][C:21]1[CH:22]=[C:17]([CH:18]=[CH:19][CH:20]=1)[CH2:23][C:6]1[N:15]([CH:32]([CH:28]2[CH2:27][CH2:26][CH2:31][CH2:30][CH2:29]2)[C:33]([NH:42][CH:36]2[CH2:41][CH2:40][CH2:39][CH2:38][CH2:37]2)=[O:35])[C:9]2[CH:10]=[CH:11][C:12]([F:14])=[CH:13][C:8]=2[N:7]=1

参加物

8

反応物 5

HCID 313Hydrochloric AcidHCID 158793-Chlorophenylacetic acidHCID 16275CyclohexanecarboxaldehydeHCID 79129Cyclohexyl isocyanideHCID 53420357N2-(tert-Butoxycarbonyl)-4-fluoro-1,2-phenylenediamine

生成物 1

HCID 673748972-[2-(3-Chloro-benzyl)-5-fluoro-benzoimidazol-1-yl]-2,N-dicyclohexyl-acetamide収率 3%

試薬・触媒・溶媒 2

HCID 887Methanol溶媒HCID 312751,4-Dioxane溶媒

実験手順

To a solution of (2-amino-5-fluoro-phenyl)-carbamic acid tert-butyl ester (33.94 mg, 0.15 mmol, 1.0 equiv; prepared as described in M. J. Bamford, M. J. Alberti, N. Bailey, S. Davies, D. K. Dean, A. Gaiba, S. Garland, J. D. Harling, D. K. Jung, T. A. Panchal, C. A. Parr, J. G. Steadman, A. K. Takle, J. T. Townsend, D. M. Wilson, J. Witherington Bioorg. Med. Chem. Lett. 2005, 15, 3402-3406) in methanol (2.0 mL) was added cyclohexanecarbaldehyde (25.80 mg, 27.08 μL, 0.23 mmol, 1.5 equiv; [2043-61-0]) and the mixture stirred at rt. After 30 min, (3-chloro-phenyl)-acetic acid (34.12 mg, 0.20 mmol, 1.33 equiv; [CAS RN 1878-65-5]) and cyclohexyl isocyanide (16.38 mg, 18.41 μL, 0.15 mmol, 1.0 equiv; [931-53-3]) were added and stirring continued at rt for 2 h. A solution of 4 M HCl in dioxane (0.2 mL) was added and the reaction mixture stirred at rt overnight. Removal of the solvent mixture under reduced pressure and purification by preparative HPLC on reversed phase eluting with a gradient of acetonitrile/water provided 2.1 mg (3%) of the title compound. MS (ISP): 482.3 [M+H]+.

後処理

  1. customprepared
  2. stirringstirring
  3. waitcontinued at rt for 2 h
  4. stirringthe reaction mixture stirred at rt overnight
  5. customRemoval of the solvent mixture
  6. customunder reduced pressure and purification by preparative HPLC on reversed phase
  7. washeluting with a gradient of acetonitrile/water

出典と根拠

ORDレコード
ord-41d26d3b099141c0b33940b7f4391a5f
出典データセット
uspto-grants-2011_08
特許番号
US08008503B2

反応ノート

読み込み中…