1-Pyrrolidinecarbonyl chloride → HCID 136198989, compound

HRID 2204499Notes

Reaction equation

HRID 2204499 reaction equation
Cl.[C:2]1([C@@H:14]2[CH2:18][CH2:17][C@@H:16]([NH2:19])[CH2:15]2)[N:6]2[C:7]3[CH:13]=[CH:12][NH:11][C:8]=3[N:9]=[CH:10][C:5]2=[N:4][N:3]=1.[N:20]1([C:25](Cl)=[O:26])[CH2:24][CH2:23][CH2:22][CH2:21]1>C1COCC1>[C:2]1([C@@H:14]2[CH2:18][CH2:17][C@@H:16]([NH:19][C:25]([N:20]3[CH2:24][CH2:23][CH2:22][CH2:21]3)=[O:26])[CH2:15]2)[N:6]2[C:7]3[CH:13]=[CH:12][NH:11][C:8]=3[N:9]=[CH:10][C:5]2=[N:4][N:3]=1

Participants

4

Reactant 2

HCID 709371-Pyrrolidinecarbonyl chlorideHCID 136395913HCID 136395913, compound

Product 1

HCID 136198989HCID 136198989, compoundYield 11.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

A round bottom flask was charged with (1R,3R)-3-(6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentanamine hydrochloride (0.150 g, 0.62 mmol, Example #D.1.4) and TEA (0.26 mL, 1.9 mmol) in THF (5.7 mL). The reaction mixture was stirred for about 5 min at ambient temperature before pyrrolidine-1-carbonyl chloride (0.052 mL, 0.46 mmol) was added. The reaction was heated at about 60° C. for about 16 h, cooled to ambient temperature, and concentrated under reduced pressure. The crude product was dissolved in DCM (40 mL) and washed with saturated aqueous NaHCO3 (20 mL), brine (20 mL), dried over anhydrous MgSO4, filtered and concentrated under reduced pressure. The material was purified by RP-HPLC (Table 2, Method i). The appropriate fractions were combined, the solvent was mostly removed under reduced pressure, and the solid was filtered and dried under lyophilization to give N-((1R,3R)-3-(6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentyl)pyrrolidine-1-carboxamide (0.018 g, 8%): LC/MS (Table 2, Method a) Rt=1.40 min; MS m/z 340 (M+H)+.

Workup

  1. additionwas added
  2. temperaturecooled to ambient temperature
  3. concentrationconcentrated under reduced pressure
  4. dissolutionThe crude product was dissolved in DCM (40 mL)
  5. washwashed with saturated aqueous NaHCO3 (20 mL), brine (20 mL)
  6. dry with materialdried over anhydrous MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe material was purified by RP-HPLC (Table 2, Method i)
  10. customthe solvent was mostly removed under reduced pressure
  11. filtrationthe solid was filtered
  12. customdried under lyophilization

Sources & evidence

ORD record
ord-360e2871d1a4421ba1e2579d36c4ede6
Source dataset
uspto-grants-2016_06
Patent number
US09365579B2

Reaction notes

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