Trifluoroacetic acid → 5-(Tert-butoxycarbonylamino-methyl)-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-benzoic acid

HRID 20775노트

반응식

HRID 20775 반응식
[C:1](=[O:8])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])[NH2:2].FC(F)(F)C(O)=O.C([SiH](CC)CC)C.[F:23][C:24]1[C:25]([NH:36][C:37]2[CH:42]=[CH:41][C:40]([I:43])=[CH:39][C:38]=2[F:44])=[C:26]([CH:30]=[C:31]([CH:34]=O)[C:32]=1[F:33])[C:27]([OH:29])=[O:28]>C(#N)C>[C:4]([O:3][C:1]([NH:2][CH2:34][C:31]1[C:32]([F:33])=[C:24]([F:23])[C:25]([NH:36][C:37]2[CH:42]=[CH:41][C:40]([I:43])=[CH:39][C:38]=2[F:44])=[C:26]([CH:30]=1)[C:27]([OH:29])=[O:28])=[O:8])([CH3:7])([CH3:6])[CH3:5]

참가 물질

6

반응물 4

HCID 6422Trifluoroacetic acidHCID 12052TriethylsilaneHCID 77922tert-Butyl carbamateHCID 231323253,4-Difluoro-2-(2-fluoro-4-iodophenylamino)-5-formyl-benzoic acid

생성물 1

HCID 866343665-(Tert-butoxycarbonylamino-methyl)-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-benzoic acid

시약·촉매·용매 1

HCID 6342Acetonitrile용매

실험 절차

tert-Butyl carbamate (commercially available, 187 mg, 1.602 mmol), trifluoroacetic acid (123 μL, 1.602 mmol), and triethylsilane (255 μL, 1.602 mmol) were added sequentially to a suspension of 3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-5-formyl-benzoic acid (225 mg, 0.534 mmol) obtained in Step A of Example 5 in acetonitrile (anhydrous, 20 mL). The mixture was stirred at room temperature for 5 days. After completion of the reaction, the reaction mixture was evaporated under reduced pressure, and the resultant residue was extracted with ethyl acetate. The organic layer was washed sequentially with water and saturated brine, dried over anhydrous sodium sulfate, and evaporated under reduced pressure. The resultant crude product was purified by silica gel flash chromatography (Mega Bond Elut, Varian, 5% methanol/methylene chloride as an eluent) to give 5-(tert-butoxycarbonylamino-methyl)-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-benzoic acid. [LC/MS m/z 523 (M+1)]. Then, trifluoroacetic acid (0.5 mL) was added to a solution of the resultant product in methylene chloride (20 mL), and the mixture was stirred at room temperature for 14 hours. After completion of the reaction, the reaction mixture was evaporated under reduced pressure, and the resultant residue was recrystallized from a mixed solvent of diethyl ether:hexane (1:1) to give 5-aminomethyl-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-benzoic acid trifluoroacetate (285 mg, 99% in 2 steps) as white crystals.

후처리

  1. customAfter completion of the reaction
  2. customthe reaction mixture was evaporated under reduced pressure
  3. extractionthe resultant residue was extracted with ethyl acetate
  4. washThe organic layer was washed sequentially with water and saturated brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. customevaporated under reduced pressure
  7. customThe resultant crude product was purified by silica gel flash chromatography (Mega Bond Elut, Varian, 5% methanol/methylene chloride as an eluent)

출처 및 근거

ORD 기록
ord-d3834cde6e9a48358b38e54b0a1ac5b8
출처 데이터셋
uspto-grants-2010_06
특허 번호
US07745663B2

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