Trifluoroacetic acid → HCID 86670406, compound

HRID 1972612Notes

Reaction equation

HRID 1972612 reaction equation
[CH3:1][CH:2]([N:4]([CH2:9][C@@H:10]1[N:15]([C:16]2[N:21]=[CH:20][C:19]([C:22]([OH:31])([C:27]([F:30])([F:29])[F:28])[C:23]([F:26])([F:25])[F:24])=[CH:18][N:17]=2)[CH2:14][CH2:13][N:12](C(OC(C)(C)C)=O)[CH2:11]1)[S:5]([CH3:8])(=[O:7])=[O:6])[CH3:3].C(O)(C(F)(F)F)=O.[Cl:46][C:47]1[N:52]=[CH:51][C:50]([S:53](Cl)(=[O:55])=[O:54])=[CH:49][CH:48]=1>C(Cl)Cl>[Cl:46][C:47]1[N:52]=[CH:51][C:50]([S:53]([N:12]2[CH2:13][CH2:14][N:15]([C:16]3[N:17]=[CH:18][C:19]([C:22]([OH:31])([C:23]([F:25])([F:26])[F:24])[C:27]([F:29])([F:30])[F:28])=[CH:20][N:21]=3)[C@@H:10]([CH2:9][N:4]([CH:2]([CH3:3])[CH3:1])[S:5]([CH3:8])(=[O:6])=[O:7])[CH2:11]2)(=[O:55])=[O:54])=[CH:49][CH:48]=1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 27927922-Chloro-5-pyridinesulfonyl chlorideHCID 86670405HCID 86670405, compound

Product 1

HCID 86670406HCID 86670406, compoundYield 96.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A 5-mL vial was charged with tert-butyl (3R)-3-(((1-methylethyl)(methylsulfonyl)amino)methyl)-4-(5-(2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl)-2-pyrimidinyl)-1-piperazinecarboxylate (0.150 g, 0.259 mmol, step 2), TFA (1.0 mL, 13 mmol) and CH2Cl2 (2 mL). The reaction mixture was stirred at room temperature for 30 min and then the volatiles were removed in vacuo. To the resulting residue was added CH2Cl2 (2 mL) followed by TEA (0.40 mL, 2.9 mmol). The mixture was stirred at room temperature for 10 min and then 6-chloropyridine-3-sulfonyl chloride (0.0627 g, 0.296 mmol, Organic Process Research & Development 2009, 13, 875) was added. After 10 min at room temperature, the mixture was concentrated and the crude product was purified by column chromatography (25 g of silica gel, 0 to 50% EtOAc in hexanes) to afford N-(((2R)-4-((6-chloro-3-pyridinyl)sulfonyl)-1-(5-(2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl)-2-pyrimidinyl)-2-piperazinyl)methyl)-N-(1-methylethyl)methanesulfonamide (0.163 g) as a light-yellow solid.

Workup

  1. customthe volatiles were removed in vacuo
  2. additionTo the resulting residue was added CH2Cl2 (2 mL)
  3. stirringThe mixture was stirred at room temperature for 10 min
  4. waitAfter 10 min at room temperature
  5. concentrationthe mixture was concentrated
  6. customthe crude product was purified by column chromatography (25 g of silica gel, 0 to 50% EtOAc in hexanes)

Sources & evidence

ORD record
ord-2aec2c6a56e54aa9ba42c5b2dc1b45a7
Source dataset
uspto-grants-2013_04
Patent number
US08431563B2

Reaction notes

Loading…