Hydrochloric Acid → (1aR,5aR)-2-(4-chloro-pyridin-2-yl)-1a,2,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene-4-carboxylic acid

HRID 1623982Notes

Reaction equation

HRID 1623982 reaction equation
C([O:3][C:4]([C:6]1[C:7]2[CH2:8][C@H:9]3[CH2:21][C@H:10]3[C:11]=2[N:12]([C:14]2[CH:19]=[C:18](I)[CH:17]=[CH:16][N:15]=2)[N:13]=1)=[O:5])C.[ClH:22]>C(#N)C>[Cl:22][C:18]1[CH:17]=[CH:16][N:15]=[C:14]([N:12]2[C:11]3[C@@H:10]4[CH2:21][C@@H:9]4[CH2:8][C:7]=3[C:6]([C:4]([OH:3])=[O:5])=[N:13]2)[CH:19]=1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 68182299(1aR,5aR)-2-(4-iodo-pyridin-2-yl)-1a,2,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene-4-carboxylic acid ethyl ester

Product 1

HCID 68182318(1aR,5aR)-2-(4-chloro-pyridin-2-yl)-1a,2,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene-4-carboxylic acid

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of (1aR,5aR)-2-(4-iodo-pyridin-2-yl)-1a,2,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene-4-carboxylic acid ethyl ester (1.0 g, 2.53 mmol) in acetonitrile (30 mL) was added concentrated HCl solution (2 mL). The reaction was stirred at 80° C. for 20 h. After removal of acetonitrile, the aqueous residue was diluted with water and a NaHCO3 solution was added to adjust the pH to 2-3. The resulting mixture was extracted with EtOAc (100 mL). The organic layer was washed with brine, dried over MgSO4, and concentrated. The residue was dissolved in a mixture of THF/MeOH/H2O (20/20/10) and added LiOH (61 mg). The reaction was stirred overnight and concentrated. The aqueous residue was diluted with water and an HCl solution was added to adjust the pH to 2-3. The resulting solid was filtered, washed with water and dried to give the title compound (610 mg). LCMS m/z=276.1 [M+H]+; 1H NMR (400 MHz, DMSO-d6) δ 0.40 (dd, J=7.7, 4.5 Hz, 1H), 1.25 (td, J=7.9, 4.6 Hz, 1H), 2.25-2.30 (m, 1H), 2.71-2.75 (m, 1H), 2.76 (d, J=16.8 Hz, 1H), 2.87 (dd, J=16.4, 6.4 Hz, 1H), 7.55 (dd, J=5.4, 1.9 Hz, 1H), 7.90 (d, J=1.8 Hz, 1H), 8.52 (d, J=5.4 Hz, 1H), 12.98 (s, 1H).

Workup

  1. customAfter removal of acetonitrile
  2. additionthe aqueous residue was diluted with water
  3. additiona NaHCO3 solution was added
  4. extractionThe resulting mixture was extracted with EtOAc (100 mL)
  5. washThe organic layer was washed with brine
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated
  8. dissolutionThe residue was dissolved in a mixture of THF/MeOH/H2O (20/20/10)
  9. additionadded LiOH (61 mg)
  10. stirringThe reaction was stirred overnight
  11. concentrationconcentrated
  12. additionThe aqueous residue was diluted with water
  13. additionan HCl solution was added
  14. filtrationThe resulting solid was filtered
  15. washwashed with water
  16. customdried

Sources & evidence

ORD record
ord-42383dd8f9044fd2b218e48bd9a6efac
Source dataset
uspto-grants-2014_07
Patent number
US08778950B2

Reaction notes

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