Trifluoroacetic acid → HCID 58438590, 화합물

HRID 1898648노트

반응식

HRID 1898648 반응식
C(O[C:6](=[O:20])[NH:7][C@H:8]([CH:17]1[CH2:19][CH2:18]1)[C:9]([N:11]1[CH2:14][CH:13]([C:15]#[N:16])[CH2:12]1)=[O:10])(C)(C)C.FC(F)(F)C(O)=O.[Br:28][C:29]1[N:30]=[C:31]2[C:37](C(O)=O)=[CH:36][N:35]([CH2:41][O:42][CH2:43][CH2:44][Si:45]([CH3:48])([CH3:47])[CH3:46])[C:32]2=[N:33][CH:34]=1.F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C>ClCCl.C(OCC)(=O)C.O>[C:15]([CH:13]1[CH2:12][N:11]([C:9](=[O:10])[C@H:8]([NH:7][C:6]([C:37]2[C:31]3[C:32](=[N:33][CH:34]=[C:29]([Br:28])[N:30]=3)[N:35]([CH2:41][O:42][CH2:43][CH2:44][Si:45]([CH3:48])([CH3:47])[CH3:46])[CH:36]=2)=[O:20])[CH:17]2[CH2:18][CH2:19]2)[CH2:14]1)#[N:16]

참가 물질

9

반응물 5

HCID 6422Trifluoroacetic acidHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 584385252-bromo-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acidHCID 67385839[(R)-2-(3-cyano-azetidin-1-yl)-1-cyclopropyl-2-oxo-ethyl]-carbamic acid tert-butyl ester

생성물 1

HCID 58438590HCID 58438590, 화합물수율 50.7%

시약·촉매·용매 3

HCID 962Water용매HCID 6344Dichloromethane용매HCID 8857Ethyl Acetate용매

실험 절차

[(R)-2-(3-cyano-azetidin-1-yl)-1-cyclopropyl-2-oxo-ethyl]-carbamic acid tert-butyl ester (0.99 g, 3.54 mmol) was dissolved in 24 mL of dichloromethane and cooled in an ice bath. Trifluoroacetic acid (10.6 mL) was added slowly and the reaction was then stirred at room temperature. After 3 h., the reaction was judged complete by TLC and was then evaporated under high vacuum. The residue was dissolved in 34 mL of acetonitrile to which was then added 2-bromo-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (1.28 g, 3.44 mmol), O-benzotriazol-1-yl-N,N,N′,N′-tetramethyluronium tetrafluoroborate (1.21 g, 3.78 mmol) and N,N-diisopropylethylamine (2.1 mL, 12 mmol). The reaction was stirred for 18 h and then water and ethyl acetate were added. The layers were separated and the aqueous layer was extracted once more with ethyl acetate. The combined organic layers were washed with brine and dried over sodium sulfate. After evaporation, the residue was purified by silica gel chromatography (methanol/dichloromethane). The resultant viscous oil was triturated with hexanes to provide 0.93 g (50%) of 2-bromo-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-cyclopropyl-2-oxo-ethyl]-amide as a white solid.

후처리

  1. temperaturecooled in an ice bath
  2. customwas then evaporated under high vacuum
  3. dissolutionThe residue was dissolved in 34 mL of acetonitrile to which
  4. stirringThe reaction was stirred for 18 h
  5. customThe layers were separated
  6. extractionthe aqueous layer was extracted once more with ethyl acetate
  7. washThe combined organic layers were washed with brine
  8. dry with materialdried over sodium sulfate
  9. customAfter evaporation
  10. customthe residue was purified by silica gel chromatography (methanol/dichloromethane)
  11. customThe resultant viscous oil was triturated with hexanes

출처 및 근거

ORD 기록
ord-6e5d75a12d1e4771b8b4f8eeefe610fb
출처 데이터셋
uspto-grants-2013_08
특허 번호
US08518945B2

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