Water → HCID 46908671, compound

HRID 1258398Notes

Reaction equation

HRID 1258398 reaction equation
[NH2:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([S:12][CH2:13][C:14]([OH:16])=[O:15])=[CH:4][CH:3]=1.N1C=CC=CC=1.O.[S:24]1[CH:28]=[CH:27][CH:26]=[C:25]1[S:29](Cl)(=[O:31])=[O:30]>C1COCC1>[S:24]1[CH:28]=[CH:27][CH:26]=[C:25]1[S:29]([NH:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([S:12][CH2:13][C:14]([OH:16])=[O:15])=[CH:4][CH:3]=1)(=[O:31])=[O:30]

Participants

6

Reactant 4

HCID 962WaterHCID 1049Pyridine2×HCID 855182-Thiophenesulfonyl chlorideHCID 46908670HCID 46908670, compound

Product 1

HCID 46908671HCID 46908671, compoundYield 58.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

32.5 mg 21 was dissolved in 1 ml THF, to which at 0° C. was added 0.28 ml pyridine solution (0.5 M in THF) followed by 0.5 ml water. Upon stirring, 25.6 mg thiophene-2-sulfonyl chloride in 1 ml THF was added dropwise. Additional 0.28 ml pyridine solution was added. The resulting solution was stirred vigorously at 0° C. and slowly warmed to room temperature. After 4 hours, the organic solvent was removed. The aqueous portion was diluted with 10 ml water and acidified at 0° C. with NaHSO4 solution (0.5 M). The mixture was extracted with ethyl acetate. The organic phase was combined, washed with water and brine and dried over Na2SO4. After removal of Na2SO4, the organic phase was concentrated and the crude product was purified via flash chromatography (5 g silica gel, DCM/CH3OH=20:1) affording 31 mg (58.4%) grey solid. 1H NMR (400 MHz, CD3CN) δ 8.36 (d, J=8.4 Hz, 1H), 8.00 (d, J=8.5 Hz, 1H), 7.68 (dd, J=5.0, 1.3 Hz, 1H), 7.62 (ddd, J=8.3, 6.8, 1.2 Hz, 1H), 7.54 (m, 2H), 7.43 (dd, J=3.8, 1.3 Hz, 1H), 7.28 (d, J=7.9 Hz, 1H), 7.04 (dd, J=5.0, 3.8 Hz, 1H), 3.78 (s, 2H). LRMS (ES−) 378 (M−H)−; HRMS (ES−) m/z calculated for C16H12NO4S3 (M−H)− 377.9934, found 377.9937.

Workup

  1. stirringThe resulting solution was stirred vigorously at 0° C.
  2. customthe organic solvent was removed
  3. additionThe aqueous portion was diluted with 10 ml water
  4. customacidified at 0° C. with NaHSO4 solution (0.5 M)
  5. extractionThe mixture was extracted with ethyl acetate
  6. washwashed with water and brine
  7. dry with materialdried over Na2SO4
  8. customAfter removal of Na2SO4
  9. concentrationthe organic phase was concentrated
  10. customthe crude product was purified via flash chromatography (5 g silica gel, DCM/CH3OH=20:1)

Sources & evidence

ORD record
ord-e1a71629699b498d97aaa955e7da576c
Source dataset
uspto-grants-2013_06
Patent number
US08466157B2

Reaction notes

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