Trifluoroacetic acid → HCID 58438590, compound

HRID 1898628Notes

Reaction equation

HRID 1898628 reaction equation
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]

Participants

9

Reactant 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 67385839HCID 67385839, compound

Product 1

HCID 58438590HCID 58438590, compoundYield 50.7%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

[(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.

Workup

  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

Sources & evidence

ORD record
ord-34c42944b9644e7db30d654043a369b4
Source dataset
uspto-grants-2013_08
Patent number
US08518945B2

Reaction notes

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