Hydrochloric Acid → HCID 9891837, compound

HRID 2227393Notes

Reaction equation

HRID 2227393 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([C:9]([NH:35]S(C(C)(C)C)=O)([C:29]2[N:33]([CH3:34])[CH:32]=[N:31][CH:30]=2)[CH2:10][CH2:11][CH2:12][N:13]2[CH2:18][CH2:17][N:16]([S:19]([C:22]3[CH:27]=[CH:26][CH:25]=[C:24]([OH:28])[CH:23]=3)(=[O:21])=[O:20])[CH2:15][CH2:14]2)=[CH:5][C:4]=1F)#[N:2].C([O-])([O-])=O.[Cs+].[Cs+].Cl.C(O)(C(F)(F)F)=O>CN(C=O)C.CO.O1CCOCC1>[NH2:35][C:9]1([C:29]2[N:33]([CH3:34])[CH:32]=[N:31][CH:30]=2)[CH2:10][CH2:11][CH2:12][N:13]2[CH2:18][CH2:17][N:16]([CH2:15][CH2:14]2)[S:19](=[O:20])(=[O:21])[C:22]2=[CH:23][C:24](=[CH:25][CH:26]=[CH:27]2)[O:28][C:8]2=[CH:7][C:6]1=[CH:5][CH:4]=[C:3]2[C:1]#[N:2]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 6422Trifluoroacetic acidHCID 10796Cesium carbonateHCID 18473236HCID 18473236, compound

Product 1

HCID 9891837HCID 9891837, compound

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6228DimethylformamideSolventHCID 312751,4-DioxaneSolvent

Procedure

N-[1-(4-cyano-3-fluorophenyl)-4-{4-[(3-hydroxyphenyl)sulfonyl]piperazin-1-yl}-1-(1-methyl-1H-imidazol-5-yl)butyl]-2-methylpropane-2-sulfinamide (0.115 g, 0.186 mmol) was dissolved in DMF (19 mL) and treated with Cs2CO3 (0.304 g, 0.93 mmol). After 24 h at 80° C., the reaction mixture was concentrated in vacuo, partitioned between CH2Cl2 and H2O, the aqueous layer washed with CH2Cl2 (2×), the organic layers combined, washed with brine, and dried (MgSO4). Filtration and concentration in vacuo gave the protected product which was dissolved in MeOH (10 mL) and treated with 4M HCl in dioxane (5 mL) with stirring. After 15 min. the reaction mixture was concentrated in vacuo, dissolved in H2O: 0.1% TFA (3 mL), and purified by RP LC on a Delta PrepPak eluting with 95:5 to 5:95 H2O(0.1% TFA): CH3CN(0.1% TFA) and lyophilized to give the product as the TFA salt of a mixture of enantiomers. This product was chromatographed on a Chiralcel OD column eluting with 0.1% DEA:hexane/EtOH, 60/40 to give the title compound as a single enantiomer. MS (M+1) 493.

Workup

  1. concentrationthe reaction mixture was concentrated in vacuo
  2. custompartitioned between CH2Cl2 and H2O
  3. washthe aqueous layer washed with CH2Cl2 (2×)
  4. washwashed with brine
  5. dry with materialdried (MgSO4)
  6. filtrationFiltration and concentration in vacuo
  7. customgave the protected product which
  8. concentrationAfter 15 min. the reaction mixture was concentrated in vacuo
  9. dissolutiondissolved in H2O
  10. custom0.1% TFA (3 mL), and purified by RP LC on a Delta PrepPak
  11. washeluting with 95:5 to 5:95 H2O(0.1% TFA)
  12. customto give the product
  13. customThis product was chromatographed on a Chiralcel OD column
  14. washeluting with 0.1% DEA

Sources & evidence

ORD record
ord-3a410f8c5ef34d8f9bc15923efcce826
Source dataset
uspto-grants-2002_07
Patent number
US06413964B1

Reaction notes

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