Trifluoroacetic acid → 2-cyclopropyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [1-(1-hydroxy-1-methyl-ethyl)-cyclopentyl]-amide

HRID 2191560Notes

Reaction equation

HRID 2191560 reaction equation
[OH:1][C:2]([C:5]1([NH:10][C:11]([C:13]2[C:21]3[C:16](=[N:17][CH:18]=[C:19]([CH:22]4[CH2:24][CH2:23]4)[N:20]=3)[N:15](COCC[Si](C)(C)C)[CH:14]=2)=[O:12])[CH2:9][CH2:8][CH2:7][CH2:6]1)([CH3:4])[CH3:3].FC(F)(F)C(O)=O>C(Cl)Cl>[OH:1][C:2]([C:5]1([NH:10][C:11]([C:13]2[C:21]3[C:16](=[N:17][CH:18]=[C:19]([CH:22]4[CH2:23][CH2:24]4)[N:20]=3)[NH:15][CH:14]=2)=[O:12])[CH2:9][CH2:8][CH2:7][CH2:6]1)([CH3:3])[CH3:4]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 67002193HCID 67002193, compound

Product 1

HCID 547555042-cyclopropyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [1-(1-hydroxy-1-methyl-ethyl)-cyclopentyl]-amideYield 53.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

In a 10 mL round-bottomed flask, 2-cyclopropyl-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [1-(1-hydroxy-1-methyl-ethyl)-cyclopentyl]-amide (207 mg, 0.45 mmol) was dissolved in CH2Cl2 (5 mL). Trifluoroacetic acid (1.7 mL) was added and the light yellow reaction mixture was stirred at room temperature for 2 h then concentrated. The residue was taken up in toluene (5 mL), concentrated and then dried under high vacuum. The residue was dissolved in CH2Cl2 (2.5 mL) and ethylenediamine (2.5 mL) was added. The reaction mixture was stirred at room temperature for 1 h then H2O and EtOAc were added. The aqueous layer was extracted with EtOAc. The combined organics were washed with H2O and brine, dried over Na2SO4 and concentrated. The residue was purified by chromatography over 12 g of SiO2 using EtOAc/hexanes (gradient: 0-90% EtOAc) to afford 79 mg (53%) of 2-cyclopropyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [1-(1-hydroxy-1-methyl-ethyl)-cyclopentyl]-amide as a white solid. MS: (M+H)+=329; mp=232.0-234.0.

Workup

  1. concentrationthen concentrated
  2. concentrationconcentrated
  3. customdried under high vacuum
  4. dissolutionThe residue was dissolved in CH2Cl2 (2.5 mL)
  5. additionethylenediamine (2.5 mL) was added
  6. stirringThe reaction mixture was stirred at room temperature for 1 h
  7. additionH2O and EtOAc were added
  8. extractionThe aqueous layer was extracted with EtOAc
  9. washThe combined organics were washed with H2O and brine
  10. dry with materialdried over Na2SO4
  11. concentrationconcentrated
  12. customThe residue was purified by chromatography over 12 g of SiO2

Sources & evidence

ORD record
ord-87ab6b5409764baf8a143b4e4515ae13
Source dataset
uspto-grants-2012_12
Patent number
US08329699B2

Reaction notes

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