Thionyl Chloride → {(S)-1-Methyl-2-[7-(4-pyridin-2-yl-piperazin-1-ylmethyl)-furo[2,3-g]indazol-1-yl]-ethyl}-carbamic acid benzyl ester

HRID 1453905Notes

Reaction equation

HRID 1453905 reaction equation
[CH2:1]([O:8][C:9](=[O:29])[NH:10][C@@H:11]([CH3:28])[CH2:12][N:13]1[C:21]2[C:16](=[CH:17][CH:18]=[C:19]3[O:24][C:23]([C:25](=O)[NH2:26])=[CH:22][C:20]3=2)[CH:15]=[N:14]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.S(Cl)(Cl)=O.[N:34]1[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=1[N:40]1[CH2:45][CH2:44]N[CH2:42][CH2:41]1>ClCCl>[CH2:1]([O:8][C:9](=[O:29])[NH:10][C@@H:11]([CH3:28])[CH2:12][N:13]1[C:21]2[C:16](=[CH:17][CH:18]=[C:19]3[O:24][C:23]([CH2:25][N:26]4[CH2:44][CH2:45][N:40]([C:35]5[CH:36]=[CH:37][CH:38]=[CH:39][N:34]=5)[CH2:41][CH2:42]4)=[CH:22][C:20]3=2)[CH:15]=[N:14]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 24386Thionyl ChlorideHCID 944591-(2-Pyridyl)piperazine2×HCID 68854663[(S)-2-(7-Carbamoyl-furo[2,3-g]indazol-1-yl)-1-methylethyl]-carbamic acid benzyl ester

Product 1

HCID 68855425{(S)-1-Methyl-2-[7-(4-pyridin-2-yl-piperazin-1-ylmethyl)-furo[2,3-g]indazol-1-yl]-ethyl}-carbamic acid benzyl esterYield 84.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of the product from Example 3, Step B (0.18 g, 0.475 mmol) in dichloromethane (20 mL) was cooled (ice bath) and thionyl chloride (0.052 mL, 0.71 mmol) added. The mixture was stirred for 30 min and then evaporated to a residue which was dissolved in dichloromethane (20 mL); this solution was evaporated and the residue dried under a vacuum. The residue was dissolved in dichloromethane (20 mL) and 1-(2-pyridyl)piperazine (0.5 mL, 3.4 mmol) was added, and the mixture was stirred at room temperature for one hour at which point additional 1-(2-pyridyl)piperazine (0.9 mL) was added. Solvent was removed by evaporation (45° C.) and THF (10 mL) was added, followed by heating the mixture at reflux temperature for one hour. This reaction mixture was evaporated and the residue dissolved in methanol (25 mL) and triethylamine (1.5 mL) followed by evaporation of this mixture to a residue which was purified by chromatography (silica gel, hexane/ethyl acetate) to give a foamy solid (0.21 g, 84%): LC/MS m/z 525 [M+H]+.

Workup

  1. additionadded
  2. customevaporated to a residue which
  3. dissolutionwas dissolved in dichloromethane (20 mL)
  4. customthis solution was evaporated
  5. customthe residue dried under a vacuum
  6. dissolutionThe residue was dissolved in dichloromethane (20 mL)
  7. additionwas added
  8. customSolvent was removed by evaporation (45° C.) and THF (10 mL)
  9. additionwas added
  10. temperatureby heating the mixture
  11. temperatureat reflux temperature for one hour
  12. customThis reaction mixture was evaporated
  13. dissolutionthe residue dissolved in methanol (25 mL)
  14. customtriethylamine (1.5 mL) followed by evaporation of this mixture to a residue which
  15. customwas purified by chromatography (silica gel, hexane/ethyl acetate)

Sources & evidence

ORD record
ord-26fcc997a8fe44ebb9139b2af8f17c1c
Source dataset
uspto-grants-2009_01
Patent number
US07476687B2

Reaction notes

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