Methanol → 2-{3-(4-Chlorophenyl)-5-oxo-4-[(2S)-3,3,3-trifluoro-2-hydroxypropyl]-4,5-dihydro-1H-1,2,4-triazol-1-yl}-N-{2-[(methylsulphonyl)amino]-2-[3-(trifluoromethyl)phenyl]ethyl}acetamide

HRID 709158Notes

Reaction equation

HRID 709158 reaction equation
[CH3:1][S:2](Cl)(=[O:4])=[O:3].Cl.[NH2:7][CH:8]([C:34]1[CH:39]=[CH:38][CH:37]=[C:36]([C:40]([F:43])([F:42])[F:41])[CH:35]=1)[CH2:9][NH:10][C:11](=[O:33])[CH2:12][N:13]1[C:17](=[O:18])[N:16]([CH2:19][C@H:20]([OH:25])[C:21]([F:24])([F:23])[F:22])[C:15]([C:26]2[CH:31]=[CH:30][C:29]([Cl:32])=[CH:28][CH:27]=2)=[N:14]1.O.CO>N1C=CC=CC=1.CS(C)=O>[Cl:32][C:29]1[CH:30]=[CH:31][C:26]([C:15]2[N:16]([CH2:19][C@H:20]([OH:25])[C:21]([F:24])([F:22])[F:23])[C:17](=[O:18])[N:13]([CH2:12][C:11]([NH:10][CH2:9][CH:8]([NH:7][S:2]([CH3:1])(=[O:4])=[O:3])[C:34]3[CH:39]=[CH:38][CH:37]=[C:36]([C:40]([F:41])([F:42])[F:43])[CH:35]=3)=[O:33])[N:14]=2)=[CH:27][CH:28]=1

Participants

7

Reactant 4

HCID 887MethanolHCID 962WaterHCID 31297Methanesulfonyl chloride2×HCID 89765105N-{2-Amino-2-[3-(trifluoromethyl)phenyl]ethyl}-2-{3-(4-chlorophenyl)-5-oxo-4-[(2S)-3,3,3-trifluoro-2-hydroxypropyl]-4,5-dihydro-1H-1,2,4-triazol-1-yl}acetamide hydrochloride

Product 1

HCID 870852502-{3-(4-Chlorophenyl)-5-oxo-4-[(2S)-3,3,3-trifluoro-2-hydroxypropyl]-4,5-dihydro-1H-1,2,4-triazol-1-yl}-N-{2-[(methylsulphonyl)amino]-2-[3-(trifluoromethyl)phenyl]ethyl}acetamide

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 1049PyridineSolvent

Procedure

4 μl (56 μmol) of methanesulphonyl chloride were added to a solution of 30 mg (51 μmol) of the compound of Example 58A in 0.5 ml of pyridine, and the mixture was stirred at RT overnight. Since HPLC analysis showed a lot of remaining starting material, further equivalents of methane-sulphonyl chloride (3.1 eq. in total) were added a little at a time until complete conversion had been achieved. 100 μl each of water and methanol were then added. After 5 min of stirring, the reaction mixture was diluted with about 3 ml of DMSO and separated by preparative HPLC [Method 8]. The product-containing fraction was freed from the solvent on a rotary evaporator and the residue was dried under high vacuum. This gave 22 mg (68% of theory) of the title compound.

Workup

  1. additionwere added a little at a time until complete conversion
  2. stirringAfter 5 min of stirring
  3. customseparated by preparative HPLC [Method 8]
  4. customThe product-containing fraction was freed from the solvent on a rotary evaporator
  5. customthe residue was dried under high vacuum

Sources & evidence

ORD record
ord-5d026a741be943ec9075dfc8f02b51a3
Source dataset
uspto-grants-2015_11
Patent number
US09180120B2

Reaction notes

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