181869-54-5 → HCID 69944079, compound

HRID 1370622Notes

Reaction equation

HRID 1370622 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:47])([O:40][CH2:41][CH:42]1[O:46][CH2:45][CH2:44][CH2:43]1)[O:37][CH2:38][I:39]>C(#N)C>[I-: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][CH2:41][CH:42]2[O:46][CH2:45][CH2:44][CH2:43]2)=[O:47])[CH:32]=[N:31]1

Participants

4

Reactant 2

HCID 3002973181869-54-5HCID 17814603Iodomethyl (2,3,4,5-tetrahydrofurfuryl) carbonate

Product 1

HCID 69944079HCID 69944079, compoundYield 50.1%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
50 °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 (0.5 g) and acetonitrile (10 ml) was added iodomethyl (2,3,4,5-tetrahydrofurfuryl) carbonate (0.594 g), and the mixture was stirred for 15 hours at 50° C. The reaction mixture was subjected to silica gel flush chromatography (eluent: ethyl acetate→acetone→acetone/ethanol=10/1), and 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 fraction containing the desired compound was concentrated and the residue 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-[(2,3,4,5-tetrahydrofurfuryl)oxycarbonyloxymethyl]-1H-1,2,4-triazolium iodide (Compound 30, 0.4 g) as a colorless powder. The product was dissolved in water (15 ml), and the solution was subjected to ion-exchange resin [Dowex 1×8 (Cl− type)]. The fraction containing the desired compound was concentrated under reduced pressure, and 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-[(2,3,4,5-tetrahydrofurfuryl)oxycarbonyloxymethyl]-1H-1,2,4-triazolium chloride (Compound 21, 0.24 g) as a colorless powder.

Workup

  1. customflush chromatography (eluent: ethyl acetate→acetone→acetone/ethanol=10/1)
  2. additionthe fraction containing the desired compound
  3. concentrationwas concentrated under reduced pressure
  4. additionThe fraction containing the desired compound
  5. concentrationwas concentrated

Sources & evidence

ORD record
ord-8b91f4ffbe28430d90955e2f0cebc192
Source dataset
uspto-grants-2003_06
Patent number
US06583164B1

Reaction notes

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