Sulfuryl chloride → HCID 18436981, compound

HRID 456925Notes

Reaction equation

HRID 456925 reaction equation
[C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[CH:12][C:13]([CH2:17][NH:18][CH2:19][CH2:20][NH:21][C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])=[CH:14][CH:15]=2)[CH:10]=[C:9]1[C:29]1[C:30](=[O:39])[NH:31][C:32]2[C:37]([CH:38]=1)=[CH:36][CH:35]=[CH:34][CH:33]=2)=[O:7])([CH3:4])([CH3:3])[CH3:2].[S:40](Cl)(Cl)(=[O:42])=[O:41].[CH:45](N(C(C)C)CC)(C)[CH3:46]>CN(C)C=O>[C:25]([O:24][C:22]([NH:21][CH2:20][CH2:19][N:18]([CH2:17][C:13]1[CH:12]=[C:11]2[C:16](=[CH:15][CH:14]=1)[N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[C:9]([C:29]1[C:30](=[O:39])[NH:31][C:32]3[C:37]([CH:38]=1)=[CH:36][CH:35]=[CH:34][CH:33]=3)=[CH:10]2)[S:40]([CH:45]=[CH2:46])(=[O:42])=[O:41])=[O:23])([CH3:28])([CH3:27])[CH3:26]

Participants

5

Reactant 3

HCID 24648Sulfuryl chlorideHCID 81531DiisopropylethylamineHCID 58817502HCID 58817502, compound

Product 1

HCID 18436981HCID 18436981, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

The amine made above 11-2 (120 mg, 0.23 mmol) was dissolved in 5.0 mL of dry N,N-dimethylformamide and allowed to stir at ambient temperature. Then sulfonyl chloride (35 μL, 0.34 mmol) and diisopropylethylamine (125 μL, 0.72 mmol) were added via pipette, respectively. The reaction was stirred for 10 hours until completion via LCMS analysis. The crude reaction solution was partitioned between ethyl acetate (15 mL) and half-saturated NaHCO3 solution (100 mL). The layers were separated and the aqueous layer was extracted several times with ethyl acetate (3×10 mL). The combined organic layers were washed with water (4×15 mL), brine, separated, dried (Na2SO4) and concentrated in vacuo to afford a yellow oil. Chromatography (SiO2, 30% to 50% ethyl acetate in hexanes) followed by concentration afforded 11-3 as a pale yellow solid; 1H NMR (300 MM, CDCl3) δ 12.73 (s, 1 H), 8.25 (d, 1H, J=8.4 Hz), 7.93 (s, 1 H), 7.62 (d, 1 H, J=7.2 Hz), 7.61 (s, 1 H), 7.50 (m, 1 H), 7.40 (d, 1 H, J=8.1 Hz), 7.39 (d, 1 H, J=8.4 Hz), 7.24 (app t, 1 H, J=7.2 Hz), 6.69 (s, 1 H), 6.43 (dd, 1 H, J=16.5, 9.6 Hz), 6.26 (d, 1 H, J=16.5 Hz), 5.94 (d, 1 H, J=9.9 Hz), 4.82 (t, 1 H, J=5.1 Hz), 4.51 (s, 2 H), 3.25 (m, 4H), 1.43 (s, 9 H), 1.39 (s, 9 H).

Workup

  1. stirringThe reaction was stirred for 10 hours until completion via LCMS analysis
  2. customThe crude reaction solution
  3. customwas partitioned between ethyl acetate (15 mL) and half-saturated NaHCO3 solution (100 mL)
  4. customThe layers were separated
  5. extractionthe aqueous layer was extracted several times with ethyl acetate (3×10 mL)
  6. washThe combined organic layers were washed with water (4×15 mL), brine
  7. customseparated
  8. dry with materialdried (Na2SO4)
  9. concentrationconcentrated in vacuo
  10. customto afford a yellow oil
  11. concentrationChromatography (SiO2, 30% to 50% ethyl acetate in hexanes) followed by concentration

Sources & evidence

ORD record
ord-f443cdfc253140e9833998ed4347c012
Source dataset
uspto-grants-2007_03
Patent number
US07186723B2

Reaction notes

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