Sodium Bicarbonate → N-(((2S)-4-((5-amino-2-thiophenyl)sulfonyl)-1-(5-(2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl)-2-pyrimidinyl)-2-piperazinyl)methyl)-N-(2-methylpropyl)methanesulfonamide

HRID 1972605Notes

Reaction equation

HRID 1972605 reaction equation
[N+:1]([C:4]1[S:8][C:7]([S:9]([N:12]2[CH2:17][CH2:16][N:15]([C:18]3[N:23]=[CH:22][C:21]([C:24]([OH:33])([C:29]([F:32])([F:31])[F:30])[C:25]([F:28])([F:27])[F:26])=[CH:20][N:19]=3)[C@@H:14]([CH2:34][N:35]([CH2:40][CH:41]([CH3:43])[CH3:42])[S:36]([CH3:39])(=[O:38])=[O:37])[CH2:13]2)(=[O:11])=[O:10])=[CH:6][CH:5]=1)([O-])=O.C([O-])(O)=O.[Na+]>[Fe].C(O)(=O)C>[NH2:1][C:4]1[S:8][C:7]([S:9]([N:12]2[CH2:17][CH2:16][N:15]([C:18]3[N:23]=[CH:22][C:21]([C:24]([OH:33])([C:25]([F:28])([F:26])[F:27])[C:29]([F:32])([F:31])[F:30])=[CH:20][N:19]=3)[C@@H:14]([CH2:34][N:35]([CH2:40][CH:41]([CH3:43])[CH3:42])[S:36]([CH3:39])(=[O:38])=[O:37])[CH2:13]2)(=[O:10])=[O:11])=[CH:6][CH:5]=1

Participants

5

Reactant 2

HCID 516892Sodium BicarbonateHCID 86670402N-(((2S)-4-((5-nitro-2-thiophenyl)sulfonyl)-1-(5-(2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl)-2-pyrimidinyl)-2-piperazinyl)methyl)-N-(2-methylpropyl)methanesulfonamide

Product 1

HCID 86670403N-(((2S)-4-((5-amino-2-thiophenyl)sulfonyl)-1-(5-(2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl)-2-pyrimidinyl)-2-piperazinyl)methyl)-N-(2-methylpropyl)methanesulfonamideYield 76.1%

Reagents, catalysts & solvents 2

HCID 23925IronCatalystHCID 176Acetic AcidSolvent

Conditions

Temperature
50 °C

Procedure

A 20-mL vial was charged with N-(((2S)-4-((5-nitro-2-thiophenyl)sulfonyl)-1-(5-(2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl)-2-pyrimidinyl)-2-piperazinyl)methyl)-N-(2-methylpropyl)methanesulfonamide (0.0916 g, 0.134 mmol), iron filings (0.0455 g, 0.815 mmol) and acetic acid (2 mL). The reaction mixture was heated at 50° C. for 20 min., then allowed to cool iii to room temperature. Saturated aqueous NaHCO3 (40 mL) was carefully added and the aqueous phase was extracted with EtOAc (2×20 mL). The combined organic extracts were washed with water (2×40 mL) and saturated aqueous NaCl (40 mL), dried over sodium sulfate, filtered and concentrated in vacuo. The crude product was purified by column chromatography (10 g of silica gel, 30 to 100% EtOAc in hexanes) to afford N-(((2S)-4-((5-amino-2-thiophenyl)sulfonyl)-1-(5-(2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl)-2-pyrimidinyl)-2-piperazinyl)methyl)-N-(2-methylpropyl)methanesulfonamide (0.0668 g) as a yellow foam.

Workup

  1. extractionthe aqueous phase was extracted with EtOAc (2×20 mL)
  2. washThe combined organic extracts were washed with water (2×40 mL) and saturated aqueous NaCl (40 mL)
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude product was purified by column chromatography (10 g of silica gel, 30 to 100% EtOAc in hexanes)

Sources & evidence

ORD record
ord-1415c5e4abda4277a766001c6ffcdef0
Source dataset
uspto-grants-2013_04
Patent number
US08431563B2

Reaction notes

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