Hydrochloric Acid → 2-(4-((2S)-4-((5-amino-1,3,4-thiadiazol-2-yl)sulfonyl)-2-methyl-1-piperazinyl)phenyl)-1,1,1-trifluoro-2-propanol

HRID 1972387Notes

Reaction equation

HRID 1972387 reaction equation
C(NC1SC(S(Cl)(=O)=O)=NN=1)(=O)C.[CH3:14][C@@H:15]1[N:20]([C:21]2[CH:26]=[CH:25][C:24]([C:27]([OH:33])([CH3:32])[C:28]([F:31])([F:30])[F:29])=[CH:23][CH:22]=2)[CH2:19][CH2:18][N:17]([S:34]([C:37]2[S:41][C:40]([NH:42][C:43](=[O:45])[CH3:44])=[N:39][N:38]=2)(=[O:36])=[O:35])[CH2:16]1.Cl>O>[CH3:14][C@@H:15]1[N:20]([C:21]2[CH:26]=[CH:25][C:24]([C:27]([OH:33])([CH3:32])[C:28]([F:30])([F:29])[F:31])=[CH:23][CH:22]=2)[CH2:19][CH2:18][N:17]([S:34]([C:37]2[S:41][C:40]([NH:42][C:43](=[O:45])[CH3:44])=[N:39][N:38]=2)(=[O:36])=[O:35])[CH2:16]1.[NH2:42][C:40]1[S:41][C:37]([S:34]([N:17]2[CH2:18][CH2:19][N:20]([C:21]3[CH:26]=[CH:25][C:24]([C:27]([OH:33])([CH3:32])[C:28]([F:30])([F:31])[F:29])=[CH:23][CH:22]=3)[C@@H:15]([CH3:14])[CH2:16]2)(=[O:35])=[O:36])=[N:38][N:39]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 128944515-(Acetylamino)-1,3,4-thiadiazole-2-sulfonyl chlorideHCID 66582468N-(5-(((3S)-3-methyl-4-(4-(2,2,2-trifluoro-1-hydroxy-1-methylethyl)phenyl)-1-piperazinyl)sulfonyl)-1,3,4-thiadiazol-2-yl)acetamide

Product 2

HCID 665823302-(4-((2S)-4-((5-amino-1,3,4-thiadiazol-2-yl)sulfonyl)-2-methyl-1-piperazinyl)phenyl)-1,1,1-trifluoro-2-propanolYield 51.5%HCID 66582468N-(5-(((3S)-3-methyl-4-(4-(2,2,2-trifluoro-1-hydroxy-1-methylethyl)phenyl)-1-piperazinyl)sulfonyl)-1,3,4-thiadiazol-2-yl)acetamide

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

N-(5-(((3S)-3-methyl-4-(4-(2,2,2-trifluoro-1-hydroxy-1-methylethyl)phenyl)-1-piperazinyl)sulfonyl)-1,3,4-thiadiazol-2-yl)acetamide was synthesized following the procedure reported for Example 30, replacing 3-furansulfonyl chloride with 5-(acetylamino)-1,3,4-thiadiazole-2-sulfonyl chloride (Eur. J. Med. Chem., 2006, 41, 918). A solution of N-(5-((3S)-3-methyl-4-(4-(1,1,1-trifluoro-2-hydroxypropan-2-yl)phenyl)piperazin-1-ylsulfonyl)-1,3,4-thiadiazol-2-yl)acetamide (85 mg, 0.172 mmol) in aqueous 5N HCl (5 mL, 5.00 mmol) was heated to 100° C. for 3 h. The mixture was diluted with water (20 mL) and extracted with EtOAc (3×100 mL). The organic layer was separated, dried (Na2SO4), filtered and concentrated. The crude material was purified by column chromatography (12 g of silica, 0 to 100% (10% [2M ammonia in methanol]/CH2Cl2) in CH2Cl2) to yield 2-(4-((2S)-4-((5-amino-1,3,4-thiadiazol-2-yl)sulfonyl)-2-methyl-1-piperazinyl)phenyl)-1,1,1-trifluoro-2-propanol (20 mg) as a mixture of 2 isomers.

Workup

  1. extractionextracted with EtOAc (3×100 mL)
  2. customThe organic layer was separated
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude material was purified by column chromatography (12 g of silica, 0 to 100% (10% [2M ammonia in methanol]/CH2Cl2) in CH2Cl2)

Sources & evidence

ORD record
ord-802030e6fd2842f18679e951f712dd63
Source dataset
uspto-grants-2013_04
Patent number
US08431563B2

Reaction notes

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