Tetrahydrofuran → HCID 67045406, compound

HRID 1923921Notes

Reaction equation

HRID 1923921 reaction equation
[N:1]1([C:6]([N:8]2[CH:12]=[CH:11]N=[CH:9]2)=[O:7])[CH:5]=[CH:4][N:3]=[CH:2]1.NC1[C:22]2C(=[N:18][CH:19]=[C:20]([Cl:37])[C:21]=2[N:23]2[CH2:28][CH2:27][CH2:26][C@@H:25]([NH:29][C:30](=[O:36])[O:31][C:32]([CH3:35])([CH3:34])[CH3:33])[CH2:24]2)NC=1.[CH2:38]1COCC1>CCOC(C)=O>[Cl:37][C:20]1[C:21]([N:23]2[CH2:28][CH2:27][CH2:26][C@@H:25]([NH:29][C:30](=[O:36])[O:31][C:32]([CH3:35])([CH3:34])[CH3:33])[CH2:24]2)=[C:22]2[C:5]([NH:1][C:6]([N:8]3[CH2:9][CH2:38][CH2:11][CH2:12]3)=[O:7])=[CH:4][NH:3][C:2]2=[N:18][CH:19]=1

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 682631,1'-CarbonyldiimidazoleHCID 67045610(R)-tert-butyl 1-(3-amino-5-chloro-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamate

Product 1

HCID 67045406HCID 67045406, compoundYield 74%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

Di(1H-imidazol-1-yl)methanone (2185 mg, 13.5 mmol) was added to a stirring solution of crude (R)-tert-butyl 1-(3-amino-5-chloro-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamate (986 mg, 2.70 mmol) in THF (10 mL), and the mixture was stirred at room temperature. After 18 hours, the reaction mixture was concentrated in vacuo. The residue obtained was dissolved in EtOAc (100 mL) and washed with water (4×20 mL) and brine (1×20 mL). The organic layer was separated, dried (MgSO4), filtered, and concentrated in vacuo. The residue obtained was purified by reverse phase chromatography (Biotage SP4, C-18 25M+, 15-85% CH3CN/water). The product was extracted from the aqueous phase into EtOAc (3×50 mL). The combined organic layers were washed with water (2×10 mL), dried (MgSO4), filtered, and concentrated in vacuo to provide (R)-tert-butyl 1-(5-chloro-3-(pyrrolidine-1-carboxamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamate (920 mg, 74% yield) as a solid. LCMS (APCI+) m/z 463.1 (M+H)+.

Workup

  1. concentrationthe reaction mixture was concentrated in vacuo
  2. customThe residue obtained
  3. washwashed with water (4×20 mL) and brine (1×20 mL)
  4. customThe organic layer was separated
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue obtained
  9. customwas purified by reverse phase chromatography (Biotage SP4
  10. extractionThe product was extracted from the aqueous phase into EtOAc (3×50 mL)
  11. washThe combined organic layers were washed with water (2×10 mL)
  12. dry with materialdried (MgSO4)
  13. filtrationfiltered
  14. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-4d7b459a908545ba80866fe03be92136
Source dataset
uspto-grants-2012_05
Patent number
US08178131B2

Reaction notes

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