Water → HCID 58817501, compound

HRID 456926Notes

Reaction equation

HRID 456926 reaction equation
C(O[C:6]([NH:8][CH2:9][CH2:10][N:11]([CH2:17][C:18]1[CH:19]=[C:20]2[C:24](=[CH:25][CH:26]=1)[N:23](C(OC(C)(C)C)=O)[C:22]([C:34]1[C:35](=[O:44])[NH:36][C:37]3[C:42]([CH:43]=1)=[CH:41][CH:40]=[CH:39][CH:38]=3)=[CH:21]2)[S:12]([CH:15]=C)(=[O:14])=[O:13])=O)(C)(C)C.O.CSC.FC(F)(F)C(O)=O>ClCCl>[O:13]=[S:12]1(=[O:14])[CH2:15][CH2:6][NH:8][CH2:9][CH2:10][N:11]1[CH2:17][C:18]1[CH:19]=[C:20]2[C:24](=[CH:25][CH:26]=1)[NH:23][C:22]([C:34]1[C:35](=[O:44])[NH:36][C:37]3[C:42]([CH:43]=1)=[CH:41][CH:40]=[CH:39][CH:38]=3)=[CH:21]2

Participants

6

Reactant 4

HCID 962WaterHCID 1068Dimethyl SulfideHCID 6422Trifluoroacetic acidHCID 18436981HCID 18436981, compound

Product 1

HCID 58817501HCID 58817501, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

The sulfonamide 11-3 (67 mg, 0.11 mmol) was dissolved in 3.0 mL of dichloromethane, 100 μL of water, and 150 μL of dimethyl sulfide at ambient temperature. Trifluoroacetic acid (2.0 mL) was then added via pipette to afford a dark yellow solution. The reaction was stirred for 5 hours until completion via LCMS analysis. The reaction solution was concentrated and the residue 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 (10×30 mL). The combined organic layers were washed with brine, separated, dried (Na2SO4) and concentrated in vacuo to afford a yellow solid. Reverse-phase chromatography (0.01% TFA present) (90% water to 90% acetonitrile) followed by free-base extraction into ethyl acetate and concentration afforded 11-4 as a yellow solid; 1H NMR (300 MHz, DMSO-d6) δ 12.17 (s, 1 H), 11.62 (s, 1 H), 8.55 (s, 1 H), 7.74 (d, 1 H, J=7.2 Hz), 7.53 (m, 3 H), 7.38 (d, 1 H, J=8.1 Hz), 7.32 (d, 1H, J=1.5 Hz), 7.25 (app t, 1 H, J=7.5 Hz), 7.11 (dd, 1 H, J=8.7, 1.2 Hz), 4.48 (s, 2H), 3.41 (m, 2 H), 3.05 (m, 2 H), 2.50 (m, 4 H).

Workup

  1. customat ambient temperature
  2. customto afford a dark yellow solution
  3. concentrationThe reaction solution was concentrated
  4. customthe residue partitioned between ethyl acetate (15 mL) and half-saturated NaHCO3 solution (100 mL)
  5. customThe layers were separated
  6. extractionthe aqueous layer was extracted several times with ethyl acetate (10×30 mL)
  7. washThe combined organic layers were washed with brine
  8. customseparated
  9. dry with materialdried (Na2SO4)
  10. concentrationconcentrated in vacuo
  11. customto afford a yellow solid
  12. extractionReverse-phase chromatography (0.01% TFA present) (90% water to 90% acetonitrile) followed by free-base extraction into ethyl acetate and concentration

Sources & evidence

ORD record
ord-0da4669c5ede4434a55dca8939d46d79
Source dataset
uspto-grants-2007_03
Patent number
US07186723B2

Reaction notes

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