Thionyl Chloride → [(S)-2-(7-Azidomethyl-furo[2,3-g]indazol-1-yl)-1-methylethyl]-carbamic acid benzyl ester

HRID 1453899Notes

Reaction equation

HRID 1453899 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]=[N+:35]=[N-].[Na+]>ClCCl.CS(C)=O>[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]=[N+:34]=[N-:35])=[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

Participants

6

Reactant 3

HCID 24386Thionyl ChlorideHCID 33557Sodium AzideHCID 68854663[(S)-2-(7-Carbamoyl-furo[2,3-g]indazol-1-yl)-1-methylethyl]-carbamic acid benzyl ester

Product 1

HCID 86612937[(S)-2-(7-Azidomethyl-furo[2,3-g]indazol-1-yl)-1-methylethyl]-carbamic acid benzyl ester

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 6344DichloromethaneSolvent

Procedure

A suspension of the product from Example 3, Step B (2.80 g, 7.39 mmol) in dichloromethane (30 mL) was cooled (ice bath), thionyl chloride (0.81 mL, 11.1 mmol) was added and the mixture was stirred for 30 minutes. During the reaction the white suspension dissolved to a yellow solution and then became a white suspension. The reaction was evaporated. The residue was treated with a solution of sodium azide (5 eq, 37 mmol, 2.4 g) in DMSO (40 mL, heated at 70° C. to dissolve) with stirring and let cool to room temperature for 20 minutes. The reaction was quenched with saturated aqueous sodium bicarbonate (100 mL) and extracted with dichloromethane (200 mL). The organic layer was washed with brine (100 mL), dried (MgSO4) and evaporated to give a yellow oil, 2.84 g. This residue was purified by chromatography (silica gel, hexane/ethyl acetate gradient) to give a colorless waxy residue, 2.45 g (82%) LC/MS m/z 405 [M+H]+.

Workup

  1. additionwas added
  2. customDuring the reaction the white suspension
  3. dissolutiondissolved to a yellow solution
  4. customThe reaction was evaporated
  5. stirringwith stirring
  6. customThe reaction was quenched with saturated aqueous sodium bicarbonate (100 mL)
  7. extractionextracted with dichloromethane (200 mL)
  8. washThe organic layer was washed with brine (100 mL)
  9. dry with materialdried (MgSO4)
  10. customevaporated
  11. customto give a yellow oil, 2.84 g
  12. customThis residue was purified by chromatography (silica gel, hexane/ethyl acetate gradient)
  13. customto give a colorless waxy residue, 2.45 g (82%) LC/MS m/z 405 [M+H]+

Sources & evidence

ORD record
ord-a8c0fe9a4ada4c96a1b29679f73ac363
Source dataset
uspto-grants-2009_01
Patent number
US07476687B2

Reaction notes

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