Hydrochloric Acid → HCID 58012251, compound

HRID 660949Notes

Reaction equation

HRID 660949 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]([CH2:13][CH:14](O)[CH3:15])[C:11](=[O:17])[N:10]([CH2:18][C:19]([NH:21][CH2:22][C:23]3[CH:28]=[CH:27][CH:26]=[C:25]([C:29]([F:32])([F:31])[F:30])[CH:24]=3)=[O:20])[N:9]=2)=[CH:4][CH:3]=1.CS(Cl)(=O)=O.C[O-].[Na+].Cl>N1C=CC=CC=1.C(OCC)(=O)C>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12](/[CH:13]=[CH:14]/[CH3:15])[C:11](=[O:17])[N:10]([CH2:18][C:19]([NH:21][CH2:22][C:23]3[CH:28]=[CH:27][CH:26]=[C:25]([C:29]([F:30])([F:31])[F:32])[CH:24]=3)=[O:20])[N:9]=2)=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 31297Methanesulfonyl chlorideHCID 10942334Sodium Methoxide2×HCID 58011643HCID 58011643, compound

Product 1

HCID 58012251HCID 58012251, compound

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 8857Ethyl AcetateSolvent

Procedure

22 mg (0.047 mmol) of 2-[3-(4-chlorophenyl)-4-(2-hydroxypropyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl]-N-[3-(trifluoromethyl)benzyl]-acetamide from Example 454 are dissolved in 1 ml of pyridine and treated at RT with 9.6 mg (0.084 mmol) of methanesulphonyl chloride. This is stirred for 2 hrs at RT. Next, it is diluted with 5 ml ethyl acetate and washed three times with 5 ml of 1 N hydrochloric acid each time. The organic phase is dried over sodium sulphate, filtered and concentrated in vacuo. The residue is dissolved in 1 ml of dry methanol, treated with 20 mg (0.94 mmol) of sodium methanolate, and stirred for 18 hrs at RT. To complete the reaction, a further 81 mg (0.38 mmol) of sodium methanolate are added, and the mixture is further stirred at RT for 48 hrs. The mixture is neutralised with 0.5 ml of 1 N hydrochloric acid and purified directly by preparative HPLC [Method 10]. 4.8 mg (23% of theory) of the target compound are thus obtained.

Workup

  1. washwashed three times with 5 ml of 1 N hydrochloric acid each time
  2. dry with materialThe organic phase is dried over sodium sulphate
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. dissolutionThe residue is dissolved in 1 ml of dry methanol
  6. stirringstirred for 18 hrs at RT
  7. customthe reaction
  8. stirringthe mixture is further stirred at RT for 48 hrs
  9. custompurified directly by preparative HPLC [Method 10]
  10. custom4.8 mg (23% of theory) of the target compound are thus obtained

Sources & evidence

ORD record
ord-7aedffc392484048bad1a45ccb4ccbfc
Source dataset
uspto-grants-2011_12
Patent number
US08084481B2

Reaction notes

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