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

HRID 406971노트

반응식

HRID 406971 반응식
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.C[O:27][C:28]([C:30]1[CH:31]=[C:32](B(O)O)[CH:33]=[CH:34][CH:35]=1)=[O:29].C(=O)([O-])[O-].[Na+].[Na+].[OH-].[Na+]>O1CCOCC1.O.C(OCC)(=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[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:35]=[C:30]([CH:31]=[CH:32][CH:33]=4)[C:28]([OH:29])=[O:27])=[CH:3][C:4]=3[N:8]=[CH:7]2)[CH:14]=[CH:13][CH:12]=1)=[O:17]

참가 물질

10

반응물 4

HCID 10340Sodium CarbonateHCID 14798Sodium HydroxideHCID 27347143-(Methoxycarbonyl)benzeneboronic acidHCID 67980496N-[3-(5-bromo-1H-benzimidazol-1-yl)phenyl]-N'-(2,2,2-trifluoro ethyl)urea

생성물 1

HCID 679800163-{1-[3-({[(2,2,2-trifluoroethyl)amino]carbonyl}amino)phenyl]-1H-benzimidazol-5-yl}benzoic acid

시약·촉매·용매 5

HCID 962Water촉매HCID 178418397HCID 178418397, 화합물촉매HCID 962Water용매HCID 8857Ethyl Acetate용매HCID 312751,4-Dioxane용매

실험 절차

A mixture of N-[3-(5-bromo-1H-benzimidazol-1-yl)phenyl]-N′-(2,2,2-trifluoro ethyl)urea (250.0 mg, 0.6050 mmol), [3-(methoxycarbonyl)phenyl]boronic acid (160 mg, 0.91 mmol Aldrich, Cat. No. 591130), tetrakis(triphenylphosphine)palladium(0) (40 mg, 0.04 mmol Aldrich, Cat. No. 216666) and sodium carbonate (130 mg, 1.2 mmol) in 1,4-dioxane (10 mL) and a few drops of 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., and 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, and dried over MgSO4. After filtration, the filtrate was concentrated under reduced pressure to afford the desired product. LCMS (M+H)+: m/z=455.1.

후처리

  1. temperatureThe reaction mixture was heated at 100° C
  2. temperature2 h., and 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

출처 및 근거

ORD 기록
ord-11988c35b54d45f0bea63f87135be61b
출처 데이터셋
uspto-grants-2014_06
특허 번호
US08754114B2

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