Sodium Carbonate → 2-(4-{1-[3-({[(2,2,2-trifluoroethyl)amino]carbonyl]amino)phenyl]-1H-benzimidazol-5-yl}phenyl)propanoic acid

HRID 406982ノート

反応式

HRID 406982 の反応式
Br[C:2]1[CH:25]=[CH:24][C:5]2[N:6]([C:9]3[CH:10]=[C:11]([NH:15][C:16]([NH:18][CH2:19][C:20]([F:23])([F:22])[F:21])=[O:17])[CH:12]=[CH:13][CH:14]=3)[CH:7]=[N:8][C:4]=2[CH:3]=1.CC1(C)C(C)(C)OB([C:34]2[CH:39]=[CH:38][C:37]([CH:40]([CH3:46])[C:41]([O:43]CC)=[O:42])=[CH:36][CH:35]=2)O1.C(=O)([O-])[O-].[Na+].[Na+].[OH-].[Na+]>O1CCOCC1.O.C(OCC)(=O)C.ClCCl>[F:21][C:20]([F:23])([F:22])[CH2:19][NH:18][C:16]([NH:15][C:11]1[CH:10]=[C:9]([N:6]2[C:5]3[CH:24]=[CH:25][C:2]([C:34]4[CH:39]=[CH:38][C:37]([CH:40]([CH3:46])[C:41]([OH:43])=[O:42])=[CH:36][CH:35]=4)=[CH:3][C:4]=3[N:8]=[CH:7]2)[CH:14]=[CH:13][CH:12]=1)=[O:17]

参加物

10

反応物 4

HCID 10340Sodium CarbonateHCID 14798Sodium HydroxideHCID 58539349Ethyl 2-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]propanoateHCID 67980496N-[3-(5-bromo-1H-benzimidazol-1-yl)phenyl]-N'-(2,2,2-trifluoro ethyl)urea

生成物 1

HCID 679802542-(4-{1-[3-({[(2,2,2-trifluoroethyl)amino]carbonyl]amino)phenyl]-1H-benzimidazol-5-yl}phenyl)propanoic acid

試薬・触媒・溶媒 5

HCID 962Water触媒HCID 962Water溶媒HCID 6344Dichloromethane溶媒HCID 8857Ethyl Acetate溶媒HCID 312751,4-Dioxane溶媒

実験手順

A mixture of N-[3-(5-bromo-1H-benzimidazol-1-yl)phenyl]-N′-(2,2,2-trifluoroethyl)urea (250.0 mg, 0.6050 mmol) (from Example 1, step 4), ethyl 2-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]propanoate (280 mg, 0.91 mmol), [1,1′-bis(diphenylphosphino)ferrocene]-dichloropalladium(II) complex with dichloromethane (1:1) (30 mg, 0.04 mmol, Aldrich, Cat. No. 379670) and sodium carbonate (130 mg, 1.2 mmol) in 1,4-dioxane (5 mL) and a few drops water was heated at 120° C. overnight under nitrogen. After the reaction was cooled to r.t., 1.0 M sodium hydroxide in water (2.4 mL,) was added to the above mixture. The reaction mixture was heated at 100° C. 2 h., then cooled to r.t. The reaction mixture was diluted with ethyl acetate, and extracted with 1N NaOH aqueous solution twice. The combined aqueous phases were acidified to pH˜2 with 6 M HCl aqueous solution, and then extracted with ethyl acetate twice. The combined organic phases (only the extracted portion with acidic aqueous solution) were washed with brine, dried over MgSO4. After filtration, the filtrate was concentrated under reduced pressure to afford the desired product. LCMS (M+H)+: m/z=483.1.

後処理

  1. temperatureThe reaction mixture was heated at 100° C
  2. temperature2 h., then cooled to r.t
  3. extractionextracted with 1N NaOH aqueous solution twice
  4. extractionextracted with ethyl acetate twice
  5. washThe combined organic phases (only the extracted portion with acidic aqueous solution) were washed with brine
  6. dry with materialdried over MgSO4
  7. filtrationAfter filtration
  8. concentrationthe filtrate was concentrated under reduced pressure

出典と根拠

ORDレコード
ord-409831dbf10e456c81f513359fe0638f
出典データセット
uspto-grants-2014_06
特許番号
US08754114B2

反応ノート

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