Dimethylformamide → HCID 58236672, compound

HRID 1987890Notes

Reaction equation

HRID 1987890 reaction equation
CN(C=O)C.[OH:6][CH2:7][CH2:8][N:9]1[CH2:13][CH2:12][CH2:11][CH2:10]1.[H-].[Na+].Cl[C:17]1[CH:22]=[CH:21][C:20]([N+:23]([O-])=O)=[CH:19][N:18]=1>O>[NH2:23][C:20]1[CH:21]=[CH:22][C:17]([O:6][CH2:7][CH2:8][N:9]2[CH2:13][CH2:12][CH2:11][CH2:10]2)=[N:18][CH:19]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 762881-PyrrolidineethanolHCID 783082-Chloro-5-nitropyridine

Product 1

HCID 58236672HCID 58236672, compound

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a stirred DMF solution (25 mL) containing N-(2-hydroxyethyl)pyrrolidine (2.18 g, 18.9 mmol) under N2 was added 60% NaH in mineral oil (0.76 g, 18.9 mmol). The mixture was stirred for 1 hr while gas evolution ceased. Subsequently 2-chloro-5-nitropyridine (2.0 g, 12.6 mmol) was added. After stirring overnight, the dark solution was poured into H2O (100 mL) and extracted 3× with EtOAc. The combined organic layers were washed 2× with H2O prior to drying over Na2SO4. Concentration under vacuum yielded an orange oil which was chromatographed on silica gel employing ˜10% MeOH/CH2Cl2 to elute 1.62 g of 5-nitro-2-(pyrrolidin-1-yl)-ethoxy)pyridine (54%). The above product reduced to the corresponding substituted aminopyridine by hydrogenation in an EtOH solution (20 mL) containing 10% Pd/C (0.1 g) under 60 psi of H2 for 4 hr. Upon completion the reaction was filtered prior to concentration under vacuum. The resulting dark oil was chromatographed on silica. Gradient elution (CH2CL2 to 20% MeOH/CH2Cl2) eluted 1.03 g of the title compound as a broad peak.

Workup

  1. stirringAfter stirring overnight
  2. extractionextracted 3× with EtOAc
  3. washThe combined organic layers were washed 2× with H2O
  4. dry with materialto drying over Na2SO4
  5. concentrationConcentration under vacuum
  6. customyielded an orange oil which
  7. customwas chromatographed on silica gel employing ˜10% MeOH/CH2Cl2
  8. washto elute 1.62 g of 5-nitro-2-(pyrrolidin-1-yl)-ethoxy)pyridine (54%)
  9. additioncontaining 10% Pd/C (0.1 g) under 60 psi of H2 for 4 hr
  10. filtrationUpon completion the reaction was filtered
  11. concentrationto concentration under vacuum
  12. customThe resulting dark oil was chromatographed on silica
  13. washGradient elution (CH2CL2 to 20% MeOH/CH2Cl2)
  14. washeluted 1.03 g of the title compound as a broad peak

Sources & evidence

ORD record
ord-7ede89a05c26430583c1099862692b00
Source dataset
uspto-grants-2009_06
Patent number
US07553836B2

Reaction notes

Loading…