Hydrochloric Acid → HCID 58981701, compound

HRID 1182315Notes

Reaction equation

HRID 1182315 reaction equation
[OH:1][C@H:2]([CH2:12][NH:13][S:14]([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][N:18]=1)(=[O:16])=[O:15])[CH2:3][NH:4]C(=O)OC(C)(C)C.O[C@@H](CNS(C1C=CC=CN=1)(=O)=O)CNC(=O)OC(C)(C)C.Cl.[C:46](=[O:75])(OC1C=CC([N+]([O-])=O)=CC=1)[O:47][C@H:48]([CH2:53][N:54]1[C:58]2[CH:59]=[C:60]([Cl:64])[C:61]([Cl:63])=[CH:62][C:57]=2[N:56]=[CH:55]1)[C:49]([CH3:52])([CH3:51])[CH3:50].C(N(C(C)C)CC)(C)C>O1CCOCC1.CN(C)C=O>[OH:1][C@H:2]([CH2:12][NH:13][S:14]([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][N:18]=1)(=[O:16])=[O:15])[CH2:3][NH:4][C:46](=[O:75])[O:47][C@H:48]([CH2:53][N:54]1[C:58]2[CH:59]=[C:60]([Cl:64])[C:61]([Cl:63])=[CH:62][C:57]=2[N:56]=[CH:55]1)[C:49]([CH3:50])([CH3:51])[CH3:52]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 58981729HCID 58981729, compoundHCID 86596688HCID 86596688, compoundHCID 86596689HCID 86596689, compound

Product 1

HCID 58981701HCID 58981701, compoundYield 45%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 312751,4-DioxaneSolvent2×

Procedure

To a solution of 370 mg (1.12 mmol) of tert-butyl (2S)-2-hydroxy-3-[(2-pyridinylsulfonyl)amino]propylcarbamate & tert-butyl (2R)-2-hydroxy-3-[(2-pyridinylsulfonyl)amino]propylcarbamate in 3.3 mL of anhydrous dioxane, 20 mL of a 4 N solution of hydrogen chloride in dioxane was added. The resulting solution was stirred for 60 min, during which time a white precipitate formed. The mixture was concentrated under reduced pressure and the resulting solid was dried under vacuum. A 54 mg (0.18mmol) sample of the residue was then added to a solution of 90 mg (0.2 mmol) of (1S)-1-[(5,6-dichloro-1H-benzimidazol-1-yl)methyl]-2,2-dimethylpropyl 4-nitrophenyl carbonate in 2 mL of dimethylformamide. Addition of 0.22 mL (1.12 mmol) of diisopropylethylamine resulted in a light yellow solution, which was stirred for 1 d under nitrogen, and then concentrated. The residue was then partition between ethyl acetate and a saturated aqueous sodium bicarbonate solution. The layers were separated and the organic phase was dried over anhydrous magnesium sulfate and concentrated. The residue was purified by silica gel chromatography eluting with a methanol:chloroform solution (1:9) to afford 44 mg (45%) of (1S)-1-[(5,6-dichloro-1H-benzimidazol-1-yl)methyl]-2,2-dimethylpropyl (2S)-2-hydroxy-3-[(2-pyridinylsulfonyl)amino]propylcarbamate & (1s)-1-[(5,6-dichloro-1H-benzimidazol-1-yl)methyl]-2,2-dimethylpropyl (2R)-2-hydroxy-3-[(2-pyridinylsulfonyl)amino]propylcarbamate. ES-LCMS m/z 544 (M+H) retention time=3.60 min.

Workup

  1. customformed
  2. concentrationThe mixture was concentrated under reduced pressure
  3. customthe resulting solid was dried under vacuum
  4. customresulted in a light yellow solution, which
  5. stirringwas stirred for 1 d under nitrogen
  6. concentrationconcentrated
  7. customThe residue was then partition between ethyl acetate
  8. customThe layers were separated
  9. dry with materialthe organic phase was dried over anhydrous magnesium sulfate
  10. concentrationconcentrated
  11. customThe residue was purified by silica gel chromatography
  12. washeluting with a methanol

Sources & evidence

ORD record
ord-b4476da10bcf4081b88f38a31ed12ace
Source dataset
uspto-grants-2007_10
Patent number
US07288541B2

Reaction notes

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