Isavuconazole → 1-[(2R,3R)-3-[4-(4-cyano-phenyl)-thiazol-2-yl]-2-(2,5-difluoro-phenyl)-2-hydroxy-butyl]-1H-[1,2,4]triazol-4-ium bromide

HRID 379653Notes

Reaction equation

HRID 379653 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[C@@:9]([OH:31])([CH2:25][N:26]1[CH:30]=[N:29][CH:28]=[N:27]1)[C@H:10]([C:12]1[S:13][CH:14]=[C:15]([C:17]2[CH:24]=[CH:23][C:20]([C:21]#[N:22])=[CH:19][CH:18]=2)[N:16]=1)[CH3:11].C(OC(C1C(C)=CC(C([Br:50])(C)OC(=O)CN)=CC=1C)=O)(C)(C)C>CC#N>[Br-:50].[C:21]([C:20]1[CH:23]=[CH:24][C:17]([C:15]2[N:16]=[C:12]([C@H:10]([CH3:11])[C@:9]([C:3]3[CH:4]=[C:5]([F:8])[CH:6]=[CH:7][C:2]=3[F:1])([OH:31])[CH2:25][N:26]3[CH:30]=[NH+:29][CH:28]=[N:27]3)[S:13][CH:14]=2)=[CH:18][CH:19]=1)#[N:22]

Participants

4

Reactant 2

HCID 6918485IsavuconazoleHCID 700978634-Tert-butoxycarbonyl-methyl-aminoacetoxy-3,5-dimethyl-benzyl bromide

Product 1

HCID 1784617011-[(2R,3R)-3-[4-(4-cyano-phenyl)-thiazol-2-yl]-2-(2,5-difluoro-phenyl)-2-hydroxy-butyl]-1H-[1,2,4]triazol-4-ium bromideYield 133.8%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture of 22.7 mg of 4-{2-[(1R,2R)-2-(2,5-Difluoro-phenyl)-2-hydroxy-1-methyl -3-[1,2,4]triazol-1-yl-propyl]-thiazol-4-yl}-benzonitrile and 25.0 mg of 4-tert-butoxycarbonyl-methyl-aminoacetoxy-3,5-dimethyl-benzyl bromide in CH3CN(1.5 mL) was refluxed over 15 hrs. The solvent was evaporated in vacuo and the residue was chromatographed on silica gel (Wakogel C-200, solvent:CH2Cl2/MeOH=10/1) to give 4-{4-[(tert-Butoxycarbonyl-methyl-amino)-acetoxy]-3,5 -dimethyl-benzyl)}-1-[(2R,3R)-3-[4-(4-cyano-phenyl)-thiazol-2-yl]-2-(2,5-difluoro-phenyl)-2-hydroxy-butyl]-1H-[1,2,4]triazol-4-ium bromide (36.0 mg, 84% as colorless heavy syrup);

Workup

  1. temperaturewas refluxed over 15 hrs
  2. customThe solvent was evaporated in vacuo
  3. customthe residue was chromatographed on silica gel (Wakogel C-200, solvent:CH2Cl2/MeOH=10/1)

Sources & evidence

ORD record
ord-e24690644dbd41dc9e8bc60f572af0b1
Source dataset
uspto-grants-2001_10
Patent number
US06300353B1

Reaction notes

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