Dimethyl Sulfoxide → 2,5-Anhydro-1,3,4-trideoxy-2-C-(2,4-difluorophenyl)-4-[[4-[4-[4-[1-[(1S,2S)-1-ethyl-2-(phenylmethoxy)propyl]-1,5-dihydro-5-oxo-4H-1,2,4-triazol-4-yl]phenyl]-1-piperazinyl]phenoxy]methyl]-1-(1H-1,2,4-triazol-1-yl)-D-threo-pentitol

HRID 512816Notes

Reaction equation

HRID 512816 reaction equation
[CH2:1]([O:8][C@H:9]([C@@H:11]([N:14]1[C:18](=[O:19])[N:17]([C:20]2[CH:25]=[CH:24][C:23]([N:26]3[CH2:31][CH2:30][N:29]([C:32]4[CH:37]=[CH:36][C:35]([OH:38])=[CH:34][CH:33]=4)[CH2:28][CH2:27]3)=[CH:22][CH:21]=2)[CH:16]=[N:15]1)[CH2:12][CH3:13])[CH3:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CS(C)=O.[OH-].[Na+].[N:45]1([CH2:50][C@@:51]2([C:68]3[CH:73]=[CH:72][C:71]([F:74])=[CH:70][C:69]=3[F:75])[O:55][CH2:54][C@@H:53]([CH2:56]OS(C3C=CC(C)=CC=3)(=O)=O)[CH2:52]2)[CH:49]=[N:48][CH:47]=[N:46]1>C(O)(C)C.O>[N:45]1([CH2:50][C@@:51]2([C:68]3[CH:73]=[CH:72][C:71]([F:74])=[CH:70][C:69]=3[F:75])[O:55][CH2:54][C@@H:53]([CH2:56][O:38][C:35]3[CH:36]=[CH:37][C:32]([N:29]4[CH2:28][CH2:27][N:26]([C:23]5[CH:24]=[CH:25][C:20]([N:17]6[C:18](=[O:19])[N:14]([C@@H:11]([CH2:12][CH3:13])[C@@H:9]([O:8][CH2:1][C:2]7[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=7)[CH3:10])[N:15]=[CH:16]6)=[CH:21][CH:22]=5)[CH2:31][CH2:30]4)=[CH:33][CH:34]=3)[CH2:52]2)[CH:49]=[N:48][CH:47]=[N:46]1

Participants

7

Reactant 4

HCID 679Dimethyl SulfoxideHCID 14798Sodium HydroxideHCID 108956292,5-Anhydro-1,3,4-trideoxy-2-C-(2,4-difluorophenyl)-4-((((4-methylphenyl)sulfonyl)oxy)methyl)-1-(1H-1,2,4-triazol-1-yl)-D-threo-pentitolHCID 462232972-((1S,2S)-1-Ethyl-2-(phenylmethoxy)propyl)-2,4-dihydro-4-(4-(4-(4-hydroxyphenyl)-1-piperazinyl)phenyl)-3H-1,2,4-triazol-3-one

Product 1

HCID 111365192,5-Anhydro-1,3,4-trideoxy-2-C-(2,4-difluorophenyl)-4-[[4-[4-[4-[1-[(1S,2S)-1-ethyl-2-(phenylmethoxy)propyl]-1,5-dihydro-5-oxo-4H-1,2,4-triazol-4-yl]phenyl]-1-piperazinyl]phenoxy]methyl]-1-(1H-1,2,4-triazol-1-yl)-D-threo-pentitolYield 98%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 3776IsopropanolSolvent

Conditions

Temperature
27.5 °C

Procedure

Added 1-((2S,3S)-2-(benzyloxy)pentan-3-yl)-4-(4-(4-(4-hydroxyphenyl) piperazin-1-yl)phenyl)-1H-1,2,4-triazol-5(4H)-one compound of formula-20 (35 g) to a mixture of dimethylsulfoxide (350 ml) and sodium hydroxide (3.4 g) and water (7 ml) at 25-30° C. and stirred for 45 minutes at 25-30° C. ((3S,5R)-5-((1H-1,2,4-triazol-1-yl)methyl)-5-(2,4-difluorophenyl)tetrahydrofuran-3-yl)methyl-4-methylbenzenesulfonate compound of formula-10 (31.5 g) was added to the above reaction mixture at 25-30° C. and stirred 5 hours at 25-30° C. After completion of the reaction, water was added to the reaction mixture. The reaction mixture was extracted twice with ethyl acetate. The organic layers were washed with 10% sodium chloride solution. Distilled off the solvent under reduced pressure to get the compound as residue. Dissolved the obtained residue in isopropanol (320 ml) at 45-50° C. Filtered the solid, washed with water and dried to get the title compound. Yield: 98%; Purity by HPLC: 95.1%

Workup

  1. additionwas added to the above reaction mixture at 25-30° C.
  2. additionwas added to the reaction mixture
  3. extractionThe reaction mixture was extracted twice with ethyl acetate
  4. washThe organic layers were washed with 10% sodium chloride solution
  5. distillationDistilled off the solvent under reduced pressure
  6. customto get the compound as residue
  7. filtrationFiltered the solid
  8. washwashed with water
  9. customdried

Sources & evidence

ORD record
ord-b9bdabf81b18495ea73c7ef532e2e027
Source dataset
uspto-grants-2015_08
Patent number
US09102664B2

Reaction notes

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