2-Chloro-3-nitropyridine → HCID 67001482, compound

HRID 1186232Notes

Reaction equation

HRID 1186232 reaction equation
C(N(C(C)C)CC)(C)C.Cl[C:11]1[C:16]([N+:17]([O-])=O)=[CH:15][CH:14]=[CH:13][N:12]=1.C[O:21][C:22]([CH2:24][CH:25]1[NH:30][CH2:29][CH2:28][N:27]([C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[CH2:26]1)=O.C[O-].[Na+]>CS(C)=O.O=[Pt]=O>[O:21]=[C:22]1[NH:17][C:16]2[CH:15]=[CH:14][CH:13]=[N:12][C:11]=2[N:30]2[CH2:29][CH2:28][N:27]([C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[CH2:26][CH:25]2[CH2:24]1

Participants

7

Reactant 4

HCID 796132-Chloro-3-nitropyridineHCID 81531DiisopropylethylamineHCID 2756816Methyl 4-Boc-piperazine-2-acetateHCID 10942334Sodium Methoxide

Product 1

HCID 67001482HCID 67001482, compound

Reagents, catalysts & solvents 2

HCID 345198Adams' catalystCatalystHCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
95 °C

Procedure

Diisopropylethylamine (3.03 mL, 17.34 mmol) was added to a mixture of 2-chloro-3-nitropyridine (2.75 g, 17.34 mmol) and the product of Example 22B (4.48 g, 17.34 mmol) in dimethyl sulfoxide (20 mL). The mixture was heated at 95° C. under nitrogen for 7 hours and then cooled to room temperature. Ice water (200 mL) was added, and the mixture was extracted with ethyl acetate (2×100 mL). The organic phase was washed with saturated brine (60 mL), dried (MgSO4) and concentrated under vacuum to an oil (6.81 g). This material was dissolved in methanol (400 mL), and PtO2 (25 mg, 0.11 mmol) was added. The flask was evacuated and purged with nitrogen (3 cycles) and then with hydrogen (3 cycles). The suspension was stirred under hydrogen (1 atm) for 54 hours. The flask was evacuated and purged with nitrogen (3 cycles) and the black suspension was filtered through diatomaceous earth with a methanol (2×10 mL) rinse. Sodium methoxide (Aldrich, 25% in methanol, 12.01 g, 55.6 mmol) was added to the filtrate, and the mixture was heated at reflux for 41 hours. After cooling to room temperature, the reaction mixture was concentrated under vacuum. The residue was purified by chromatography (SiO2, eluted with methanol-CH2Cl2 (0:100-5:95), followed by crystallization from ethanol (10 mL) to provide the title compound: 1H NMR (300 MHz, CDCl3) δ ppm 1.48 (s, 9H), 2.27-2.40 (m, 1H), 2.78 (dd, J=13.5, 5.9 Hz, 1H), 2.91-3.20 (m, 3H), 3.55-3.68 (m, 1H), 3.69-3.80 (m, 1H), 3.99-4.19 (m, 2H), 6.95 (dd, J=7.7, 5.0 Hz, 1H), 7.23 (dd, J=7.7, 1.4 Hz, 1H), 7.61 (s, 1H), 8.18 (dd, J=5.0, 1.8 Hz, 1H); MS (ESI) m/z 319 (M+H)+.

Workup

  1. temperaturecooled to room temperature
  2. extractionthe mixture was extracted with ethyl acetate (2×100 mL)
  3. washThe organic phase was washed with saturated brine (60 mL)
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated under vacuum to an oil (6.81 g)
  6. dissolutionThis material was dissolved in methanol (400 mL)
  7. customThe flask was evacuated
  8. custompurged with nitrogen (3 cycles)
  9. customThe flask was evacuated
  10. custompurged with nitrogen (3 cycles)
  11. filtrationthe black suspension was filtered through diatomaceous earth with a methanol (2×10 mL)
  12. washrinse
  13. temperaturethe mixture was heated
  14. temperatureat reflux for 41 hours
  15. temperatureAfter cooling to room temperature
  16. concentrationthe reaction mixture was concentrated under vacuum
  17. customThe residue was purified by chromatography (SiO2
  18. washeluted with methanol-CH2Cl2 (0:100-5:95)
  19. customfollowed by crystallization from ethanol (10 mL)

Sources & evidence

ORD record
ord-5fd08411d78648ff95227a5d8e4c58c5
Source dataset
uspto-grants-2014_03
Patent number
US08673896B2

Reaction notes

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