3-(Trifluoromethylthio)phenyl isothiocyanate → 4-[1-Methyl-2-(3-trifluoromethylsulfanyl-phenylamino)-1H-benzoimidazol-5-yloxy]-pyridine-2-carboxylic acid (2-hydroxy-ethyl)-amide

HRID 2070314노트

반응식

HRID 2070314 반응식
[F:1][C:2]([F:14])([F:13])[S:3][C:4]1[CH:5]=[C:6]([N:10]=[C:11]=S)[CH:7]=[CH:8][CH:9]=1.[OH:15][CH2:16][CH2:17][NH:18][C:19]([C:21]1[CH:26]=[C:25]([O:27][C:28]2[CH:33]=[CH:32][C:31]([NH:34][CH3:35])=[C:30]([NH2:36])[CH:29]=2)[CH:24]=[CH:23][N:22]=1)=[O:20]>CO>[OH:15][CH2:16][CH2:17][NH:18][C:19]([C:21]1[CH:26]=[C:25]([O:27][C:28]2[CH:33]=[CH:32][C:31]3[N:34]([CH3:35])[C:11]([NH:10][C:6]4[CH:7]=[CH:8][CH:9]=[C:4]([S:3][C:2]([F:14])([F:13])[F:1])[CH:5]=4)=[N:36][C:30]=3[CH:29]=2)[CH:24]=[CH:23][N:22]=1)=[O:20]

참가 물질

4

반응물 2

HCID 44110273-(Trifluoromethylthio)phenyl isothiocyanateHCID 210372884-(3-Amino-4-methylamino-phenoxy)-pyridine-2-carboxylic acid (2-hydroxy-ethyl)-amide

생성물 1

HCID 220411304-[1-Methyl-2-(3-trifluoromethylsulfanyl-phenylamino)-1H-benzoimidazol-5-yloxy]-pyridine-2-carboxylic acid (2-hydroxy-ethyl)-amide

시약·촉매·용매 1

HCID 887Methanol용매

실험 절차

A flask was charged with 3-(trifluoromethylthio)phenylisothiocyanate (1 eq), 4-(3-amino-4-methylamino-phenoxy)-pyridine-2-carboxylic acid (2-hydroxy-ethyl)-amide (1 eq), and MeOH. The reaction was maintained at rt overnight. Ferric chloride, (1.5 eq) was added and the resulting red reaction mixture was stirred overnight. The reaction was partitioned with EtOAc and water, and filtered through Celite. The layers were separated and the aqueous phase was neutralized with saturated Na2CO3 solution. The resulting aqueous phase was extracted with EtOAc and the mixture was filtered through Celite. The phases were separated and the aqueous phase was again extracted and filtered. The combined organic layers were washed with brine, dried (MgSO4), filtered, and concentrated to give a brown solid. The crude residue was purified by reverse phase HPLC. LCMS m/z 504.1 (MH+), tR=3.7 min.

후처리

  1. customThe reaction was partitioned with EtOAc and water
  2. filtrationfiltered through Celite
  3. customThe layers were separated
  4. extractionThe resulting aqueous phase was extracted with EtOAc
  5. filtrationthe mixture was filtered through Celite
  6. customThe phases were separated
  7. extractionthe aqueous phase was again extracted
  8. filtrationfiltered
  9. washThe combined organic layers were washed with brine
  10. dry with materialdried (MgSO4)
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customto give a brown solid
  14. customThe crude residue was purified by reverse phase HPLC

출처 및 근거

ORD 기록
ord-bd319419e224474d970bb600e468fea2
출처 데이터셋
uspto-grants-2012_10
특허 번호
US08299108B2

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