Oxalyl chloride → HCID 178480681, 화합물

HRID 512972노트

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HRID 512972 반응식
Cl.[CH3:2][N:3]1[CH2:8][CH2:7][N:6]([C:9]2[CH:17]=[CH:16][C:12]([C:13](O)=[O:14])=[C:11]([N:18]([C@H:25]3[CH2:30][CH2:29][C@@H:28]([O:31]C(C4C=CC=CC=4)=O)[CH2:27][CH2:26]3)C(=O)C(F)(F)F)[CH:10]=2)[CH2:5][CH2:4]1.C(Cl)(=O)C(Cl)=O.[F:46][C:47]1[CH:48]=[C:49]([CH:61]=[C:62]([F:64])[CH:63]=1)[CH2:50][C:51]1[CH:52]=[C:53]2[C:57](=[CH:58][CH:59]=1)[NH:56][N:55]=[C:54]2[NH2:60].O[Li].O>C(Cl)Cl.N1C=CC=CC=1.CO.O>[F:46][C:47]1[CH:48]=[C:49]([CH:61]=[C:62]([F:64])[CH:63]=1)[CH2:50][C:51]1[CH:52]=[C:53]2[C:57](=[CH:58][CH:59]=1)[NH:56][N:55]=[C:54]2[NH:60][C:13](=[O:14])[C:12]1[CH:16]=[CH:17][C:9]([N:6]2[CH2:7][CH2:8][N:3]([CH3:2])[CH2:4][CH2:5]2)=[CH:10][C:11]=1[NH:18][C@H:25]1[CH2:30][CH2:29][C@@H:28]([OH:31])[CH2:27][CH2:26]1

참가 물질

9

반응물 4

HCID 65578Oxalyl chlorideHCID 168937Lithium hydroxide, monohydrateHCID 441342655-[(3,5-difluorophenyl)methyl]-1H-indazol-3-amineHCID 178480699HCID 178480699, 화합물

생성물 1

HCID 178480681HCID 178480681, 화합물수율 27.2%

시약·촉매·용매 4

HCID 887Methanol용매HCID 962Water용매HCID 1049Pyridine용매HCID 6344Dichloromethane용매

실험 절차

4-(4-methylpiperazin-1-yl)-2-[{cis-4-[(phenylcarbonyl)oxy]cyclohexyl}(trifluoroacetyl)amino]benzoic acid hydrochloride (1.03 gr, 1.94 mmol) and oxalyl chloride (3.88 mmol) were stirred in DCM dry (20 mL) and a few drops of dry DMF at 0° C., temperature was allowed to reach room temperature in 2 hours. Volatiles were evaporated and the residue dissolved in dry pyridine (25 mL) at 0° C. A solution of 5-(3,5-difluoro-benzyl)-1H-indazol-3-ylamine (387 mg, 1.49 mmol) in dry pyridine (6 mL) was added to the cooled reaction mixture. Temperature was allowed to reach room temperature overnight. Reaction was quenched with NaHCO3 sat. sol and extracted with ethyl acetate. Collected organic phases were dried over Na2SO4, filtered and evaporated to dryness. Residue was purified by column chromatography over silica gel (DCM/AcOEt/EtOH=100/10/15). The so obtained derivative, was dissolved in MeOH (200 mL) and water (20 mL) and treated at 60° C. with LiOH hydrate (160 mg, 3.8 mmol) for 4 hours. MeOH was evaporated and the resulting aqueous phase was extracted with EtOAc. Collected organic phases were dried over Na2SO4, filtered and evaporated to dryness. Residue was purified by column chromatography over silica gel (DCM/EtOH/NH3 5N in MeOH=100/10/2) affording 233 mg of title compound.

후처리

  1. dry with materialdry (20 mL) and a few drops of dry DMF at 0° C.
  2. customVolatiles were evaporated
  3. dissolutionthe residue dissolved in dry pyridine (25 mL) at 0° C
  4. waitto reach room temperature overnight
  5. customReaction
  6. customwas quenched with NaHCO3 sat. sol
  7. extractionextracted with ethyl acetate
  8. dry with materialCollected organic phases were dried over Na2SO4
  9. filtrationfiltered
  10. customevaporated to dryness
  11. customResidue was purified by column chromatography over silica gel (DCM/AcOEt/EtOH=100/10/15)
  12. customThe so obtained derivative
  13. customMeOH was evaporated
  14. extractionthe resulting aqueous phase was extracted with EtOAc
  15. dry with materialCollected organic phases were dried over Na2SO4
  16. filtrationfiltered
  17. customevaporated to dryness
  18. customResidue was purified by column chromatography over silica gel (DCM/EtOH/NH3 5N in MeOH=100/10/2)

출처 및 근거

ORD 기록
ord-dccc14647a4343fca9e6755a217ce72f
출처 데이터셋
uspto-grants-2015_08
특허 번호
US09102662B2

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