181869-54-5 → HCID 69943453, compound

HRID 1370630Notes

Reaction equation

HRID 1370630 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C@@:9]([OH:35])([CH2:29][N:30]1[CH:34]=[N:33][CH:32]=[N:31]1)[C@H:10]([N:12]1[CH2:16][CH2:15][N:14]([C:17]2[CH:22]=[CH:21][C:20]([N:23]3[CH:27]=[N:26][N:25]=[N:24]3)=[CH:19][CH:18]=2)[C:13]1=[O:28])[CH3:11].[C:36](=[O:48])([O:40][C@H:41]([C:43]([O:45][CH2:46][CH3:47])=[O:44])[CH3:42])[O:37][CH2:38][Cl:39]>C(#N)C>[Cl-:39].[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C@:9]([OH:35])([C@H:10]([N:12]1[CH2:16][CH2:15][N:14]([C:17]2[CH:22]=[CH:21][C:20]([N:23]3[CH:27]=[N:26][N:25]=[N:24]3)=[CH:19][CH:18]=2)[C:13]1=[O:28])[CH3:11])[CH2:29][NH+:30]1[CH2:34][N:33]([CH2:38][O:37][C:36]([O:40][C@H:41]([C:43]([O:45][CH2:46][CH3:47])=[O:44])[CH3:42])=[O:48])[CH:32]=[N:31]1

Participants

4

Reactant 2

HCID 3002973181869-54-5HCID 12019883HCID 12019883, compound

Product 1

HCID 69943453HCID 69943453, compoundYield 30.5%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
95 °C

Procedure

To a mixture of 1-[(1R,2R)-2-(2,4-difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl]-3-[4-(1H-tetrazol-1-yl)phenyl]-2-imidazolidinone(0.50 g) and chloromethyl [(1S)-1-(ethoxycarbonyl)ethyl] carbonate(1.09 g) was added acetonitrile (5 ml), and the mixture was stirred for 68 hours at 95° C. The reaction mixture was concentrated under reduced pressure. To the residue was added diisopropyl ether (6 ml), and the resulting powder was collected by filtration. The powder was subjected to silica gel flush chromatography (eluent: ethyl acetate→ethyl acetate/acetone=1/1→acetone→acetone/ethanol=5/1). The fraction containing the desired compound was concentrated under reduced pressure. The residue was subjected to ODS column chromatography (eluent: methanol/water=3/2). The eluate was concentrated in vacuo and dissolved in water (50 ml). The solution was lyophilized to give 1-[(2R,3R)-2-(2,4-difluorophenyl)-2-hydroxy-3-[2-oxo-3-[4-(1H-tetrazol-1-yl)phenyl]-1-imidazolidinyl]butyl]-4-[[(1S)-1-ethoxycarbonylethoxy]carbonyloxymethyl]-1H-1,2,4-triazolium chloride (Compound 23,0.22 g) as a white powder.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. additionTo the residue was added diisopropyl ether (6 ml)
  3. filtrationthe resulting powder was collected by filtration
  4. customflush chromatography (eluent: ethyl acetate→ethyl acetate/acetone=1/1→acetone→acetone/ethanol=5/1)
  5. additionThe fraction containing the desired compound
  6. concentrationwas concentrated under reduced pressure
  7. concentrationThe eluate was concentrated in vacuo
  8. dissolutiondissolved in water (50 ml)

Sources & evidence

ORD record
ord-48b481ef91a34296b15e4cb44d5ce14e
Source dataset
uspto-grants-2003_06
Patent number
US06583164B1

Reaction notes

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