Trifluoroacetic acid → 2-(4-tert-butyl-pyridin-2-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(4-cyano-piperidin-1-yl)-1-cyclopropyl-2-oxo-ethyl]-amide

HRID 1898585Notes

Reaction equation

HRID 1898585 reaction equation
[C:1]([CH:3]1[CH2:8][CH2:7][N:6]([C:9](=[O:44])[C@H:10]([NH:14][C:15]([C:17]2[C:25]3[C:20](=[N:21][CH:22]=[C:23]([C:26]4[CH:31]=[C:30]([C:32]([CH3:35])([CH3:34])[CH3:33])[CH:29]=[CH:28][N:27]=4)[N:24]=3)[N:19](COCC[Si](C)(C)C)[CH:18]=2)=[O:16])[CH:11]2[CH2:13][CH2:12]2)[CH2:5][CH2:4]1)#[N:2].FC(F)(F)C(O)=O>ClCCl>[C:1]([CH:3]1[CH2:8][CH2:7][N:6]([C:9](=[O:44])[C@H:10]([NH:14][C:15]([C:17]2[C:25]3[C:20](=[N:21][CH:22]=[C:23]([C:26]4[CH:31]=[C:30]([C:32]([CH3:34])([CH3:33])[CH3:35])[CH:29]=[CH:28][N:27]=4)[N:24]=3)[NH:19][CH:18]=2)=[O:16])[CH:11]2[CH2:12][CH2:13]2)[CH2:5][CH2:4]1)#[N:2]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 673859122-(4-tert-butyl-pyridin-2-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(4-cyano-piperidin-1-yl)-1-cyclopropyl-2-oxo-ethyl]-amide

Product 1

HCID 584385472-(4-tert-butyl-pyridin-2-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(4-cyano-piperidin-1-yl)-1-cyclopropyl-2-oxo-ethyl]-amideYield 63.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

In a round-bottomed flask, 2-(4-tert-butyl-pyridin-2-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(4-cyano-piperidin-1-yl)-1-cyclopropyl-2-oxo-ethyl]-amide (62 mg, 0.091 mmol) was dissolved in dichloromethane (0.5 mL) and trifluoroacetic acid (0.28 mL) was added. The yellow reaction mixture was stirred at room temperature for 2.75 h then concentrated under reduced pressure. The residue was dissolved in dichloromethane (0.5 mL) and ethylenediamine (0.37 mL) was added. The reaction mixture was stirred at room temperature for 1.25 h then quenched with 5 mL water and extracted with EtOAc (2×). The combined organic layers were washed with 5 mL water and 5 mL brine then dried over sodium sulfate, filtered and concentrated. The residue was chromatographed over 8 g SiO2 with MeOH/CH2Cl2/0.5% NH4OH (gradient: 0-4% MeOH). All fractions containing product were combined and concentrated to afford 28 mg (61%) of 2-(4-tert-butyl-pyridin-2-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(4-cyano-piperidin-1-yl)-1-cyclopropyl-2-oxo-ethyl]-amide as a yellow foamy solid. MS: (M+H)+=486.

Workup

  1. concentrationthen concentrated under reduced pressure
  2. dissolutionThe residue was dissolved in dichloromethane (0.5 mL)
  3. additionethylenediamine (0.37 mL) was added
  4. stirringThe reaction mixture was stirred at room temperature for 1.25 h
  5. customthen quenched with 5 mL water
  6. extractionextracted with EtOAc (2×)
  7. washThe combined organic layers were washed with 5 mL water and 5 mL brine
  8. dry with materialthen dried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe residue was chromatographed over 8 g SiO2 with MeOH/CH2Cl2/0.5% NH4OH (gradient: 0-4% MeOH)
  12. additionAll fractions containing product
  13. concentrationconcentrated

Sources & evidence

ORD record
ord-c2f84be59c864d0fbaff0a93ed9dc905
Source dataset
uspto-grants-2013_08
Patent number
US08518945B2

Reaction notes

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