Hydrochloric Acid → HCID 68553505, compound

HRID 1868133Notes

Reaction equation

HRID 1868133 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][N:11]([S:14]([C:17]3[S:21][C:20]([N:22]4[CH2:26][CH2:25][CH2:24][CH:23]4[C:27](O)=[O:28])=[CH:19][CH:18]=3)(=[O:16])=[O:15])[C@H:10]([CH3:30])[CH2:9]2)=[C:4]([C:31]([F:34])([F:33])[F:32])[CH:3]=1.C1N=C[N:37](C(N2C=NC=C2)=O)C=1.[NH4+].[OH-].Cl>C1COCC1.C(OCC)(=O)C>[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][N:11]([S:14]([C:17]3[S:21][C:20]([N:22]4[CH2:26][CH2:25][CH2:24][CH:23]4[C:27]([NH2:37])=[O:28])=[CH:19][CH:18]=3)(=[O:16])=[O:15])[C@H:10]([CH3:30])[CH2:9]2)=[C:4]([C:31]([F:33])([F:32])[F:34])[CH:3]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 14923Ammonium HydroxideHCID 682631,1'-CarbonyldiimidazoleHCID 68550932HCID 68550932, compound

Product 1

HCID 68553505HCID 68553505, compoundYield 31.6%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

Crude 1-(5-((R)-4-(4-fluoro-2-(trifluoromethyl)phenyl)-2-methylpiperazin-1-ylsulfonyl)thiophen-2-yl)pyrrolidine-2-carboxylic acid (570 mg, 1.094 mmol) charged to a reaction flask was dissolved in THF (23 mL). To it was added CDI (649 mg, 4.38 mmol) and the reaction mixture was heated to reflux for 1 hour. After cooling down to room temperature excess NH4OH (28% NH3)(23 ml) was added dropwise via addition funnel. The reaction mixture was left to stir at room temperature for 10 minutes, then it was diluted with ethyl acetate, acidified (pH acidic) using 10% HCl (aqueous) and stirred for 5 minutes. The layers were separated, and the organic layer washed with saturated brine, dried over MgSO4, concentrated. Crude product containing a significant amount of starting acid by TLC was subjected to the same reaction and work up conditions. After reaction completation crude was purified via flash column chromatography to yield 1-(5-((R)-4-(4-fluoro-2-(trifluoromethyl)phenyl)-2-methylpiperazin-1-ylsulfonyl)thiophen-2-yl)pyrrolidine-2-carboxamide as white solid (180 mg, 31% yield). HRMS: calcd for C21H24F4N4O3S2+H+, 521.12987. found (ESI-FTMS, [M+H]1+), 521.13026.

Workup

  1. temperaturethe reaction mixture was heated
  2. temperatureto reflux for 1 hour
  3. additionwas added dropwise via addition funnel
  4. waitThe reaction mixture was left
  5. stirringstirred for 5 minutes
  6. customThe layers were separated
  7. washthe organic layer washed with saturated brine
  8. dry with materialdried over MgSO4
  9. concentrationconcentrated
  10. additionCrude product containing a significant amount
  11. customwas subjected to the same reaction
  12. customAfter reaction completation crude
  13. customwas purified via flash column chromatography

Sources & evidence

ORD record
ord-7371c2de5ef941ff83340d16843dfa5f
Source dataset
uspto-grants-2009_12
Patent number
US07632838B2

Reaction notes

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