Sodium Bicarbonate → HCID 56932880, compound

HRID 1972597Notes

Reaction equation

HRID 1972597 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]3[CH2:40][CH2:39][NH:38][C:37](=[O:41])[C:36]3([CH3:43])[CH3:42])[CH2:13]2)(=[O:11])=[O:10])=[CH:6][CH:5]=1)([O-])=O.C([O-])(O)=O.[Na+]>[Fe].CC(O)=O>[NH2:1][C:4]1[S:8][C:7]([S:9]([N:12]2[CH2:17][CH2:16][N:15]([C:18]3[N:19]=[CH:20][C:21]([C:24]([OH:33])([C:25]([F:26])([F:28])[F:27])[C:29]([F:30])([F:31])[F:32])=[CH:22][N:23]=3)[C@@H:14]([CH2:34][N:35]3[CH2:40][CH2:39][NH:38][C:37](=[O:41])[C:36]3([CH3:43])[CH3:42])[CH2:13]2)(=[O:10])=[O:11])=[CH:6][CH:5]=1

Participants

5

Reactant 2

HCID 516892Sodium BicarbonateHCID 86670401HCID 86670401, compound

Product 1

HCID 56932880HCID 56932880, compoundYield 28%

Reagents, catalysts & solvents 2

HCID 23925IronCatalyst2×HCID 176Acetic AcidSolvent

Conditions

Temperature
50 °C

Procedure

A 250-mL round-bottomed flask was charged with 4-(((2S)-4-((5-nitro-2-thiophenyl)sulfonyl)-1-(5-(2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl)-2-pyrimidinyl)-2-piperazinyl)methyl)-3,3-dimethyl-2-piperazinone (0.314 g, 0.475 mmol, step 2), iron filings (0.136 g, 2.43 mmol) and AcOH (10 mL). The reaction mixture was heated at 50° C. for 3 h. An additional 0.052 g of iron filing was added and the heating at 50° C. was continued for 30 min. The mixture was allowed to cool to room temperature and then saturated aqueous NaHCO3 (300 mL) was slowly added. The aqueous phase was extracted with EtOAc (3×100 mL). The combined organic phases were dried over sodium sulfate, filtered and concentrated in vacuo. The crude product was purified by preparative HPLC (Phenomenex 5 μm, C18 column, 150×30 mm) eluting with 10 to 90% ACN with 0.1% TFA in H2O with 0.1% TFA in 15 min. The fractions were concentrated and basified with saturated aqueous NaHCO3. The resulting solid was collected (0.130 g). The aqueous phase was extracted with 10% iPrOH in CHCl3 containing 1% NH4OH. The combined organic extracts were dried over sodium sulfate, filtered and concentrated to obtain an additional 0.265 g. The combined material was purified by column chromatography (25 g of silica gel, 0 to 10% (2M NH3 in MeOH) in CH2Cl2 to afford 4-(((2S)-4-((5-amino-2-thiophenyl)sulfonyl)-1-(5-(2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl)-2-pyrimidinyl)-2-piperazinyl)methyl)-3,3-dimethyl-2-piperazinone (0.084 g) as an off-white solid.

Workup

  1. temperatureto cool to room temperature
  2. extractionThe aqueous phase was extracted with EtOAc (3×100 mL)
  3. dry with materialThe combined organic phases were dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude product was purified by preparative HPLC (Phenomenex 5 μm, C18 column, 150×30 mm)
  7. washeluting with 10 to 90% ACN with 0.1% TFA in H2O with 0.1% TFA in 15 min
  8. concentrationThe fractions were concentrated
  9. customThe resulting solid was collected (0.130 g)
  10. extractionThe aqueous phase was extracted with 10% iPrOH in CHCl3 containing 1% NH4OH
  11. dry with materialThe combined organic extracts were dried over sodium sulfate
  12. filtrationfiltered
  13. concentrationconcentrated
  14. customto obtain an additional 0.265 g
  15. customThe combined material was purified by column chromatography (25 g of silica gel, 0 to 10% (2M NH3 in MeOH) in CH2Cl2

Sources & evidence

ORD record
ord-875405f56848434196b023a9a5089693
Source dataset
uspto-grants-2013_04
Patent number
US08431563B2

Reaction notes

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