2-(2,4-dichloro-benzenesulfonylamino)-N-methoxy-N-methyl-5-[4-(piperidine-1-sulfonyl)-phenylsulfanyl]-isonicotinamide → N-{4-butyryl-5-[4-(piperidine-1-sulfonyl)-phenylsulfanyl]-pyridin-2-yl}-2,4-dichloro-benzenesulfonamide

HRID 1366857Notes

Reaction equation

HRID 1366857 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[S:9]([NH:12][C:13]1[CH:14]=[C:15]([C:22]([S:25][C:26]2[CH:31]=[CH:30][C:29]([S:32]([N:35]3[CH2:40][CH2:39][CH2:38][CH2:37][CH2:36]3)(=[O:34])=[O:33])=[CH:28][CH:27]=2)=[CH:23][N:24]=1)[C:16](N(OC)C)=[O:17])(=[O:11])=[O:10].[CH2:41]([Mg]Cl)[CH2:42][CH3:43]>C1COCC1>[C:16]([C:15]1[C:22]([S:25][C:26]2[CH:27]=[CH:28][C:29]([S:32]([N:35]3[CH2:40][CH2:39][CH2:38][CH2:37][CH2:36]3)(=[O:33])=[O:34])=[CH:30][CH:31]=2)=[CH:23][N:24]=[C:13]([NH:12][S:9]([C:3]2[CH:4]=[CH:5][C:6]([Cl:8])=[CH:7][C:2]=2[Cl:1])(=[O:10])=[O:11])[CH:14]=1)(=[O:17])[CH2:41][CH2:42][CH3:43]

Participants

4

Reactant 2

HCID 577181912-(2,4-dichloro-benzenesulfonylamino)-N-methoxy-N-methyl-5-[4-(piperidine-1-sulfonyl)-phenylsulfanyl]-isonicotinamideHCID 178455855HCID 178455855, compound

Product 1

HCID 57718170N-{4-butyryl-5-[4-(piperidine-1-sulfonyl)-phenylsulfanyl]-pyridin-2-yl}-2,4-dichloro-benzenesulfonamideYield 6.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

2-(2,4-Dichloro-benzenesulfonylamino)-N-methoxy-N-methyl-5-[4-(piperidine-1-sulfonyl)-phenylsulfanyl]-isonicotinamide (150 mg, 0.233 mmol) was stirred in THF (30 ml) under nitrogen at room temperature. 2M Propylmagnesium chloride (1.2 ml, 2.33 mmol) was added and the reaction stirred overnight. The reaction was quenched using 1N HCl solution partitioned between a mixture of NaHCO3 solution (30 ml) and ethyl acetate (30 ml). The organic layer was dried (MgSO4) and concentrated under reduced pressure. The residue was purified by flash column chromatography using ethyl acetate 2/3 hexane as eluent to give N -{4-butyryl-5-[4-(piperidine-1-sulfonyl)-phenylsulfanyl]-pyridin-2-yl}-2,4-dichloro-benzenesulfonamide as an off-white solid (10 mg, 6%). 1H NMR (CDCl3): 8.21 (1 H, s, Ar); 8.06 (1 H, d, Ar); 7.60 (2 H, d, Ar); 7.47 (1 H, s, Ar); 7.38 (1 H, d, Ar); 7.26 (3 H, m, py and Ar); 2.89 (4 H, m, 2×CH2N pip); 2.70 (2 H, t, COCH2); 1.56 (6 H, m, 2×CH2 pip, COCH2CH2); 1.47 (2 H, m, CH2 pip); 0.90 (3 H, t, COCH2CH2CH3). HPLC (Luna 2, Gradient 1): rt=6.92 minutes. LCMS: rt=7.61 minutes, 629 (M+H)+.

Workup

  1. customThe reaction was quenched
  2. custompartitioned between a mixture of NaHCO3 solution (30 ml) and ethyl acetate (30 ml)
  3. dry with materialThe organic layer was dried (MgSO4)
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by flash column chromatography

Sources & evidence

ORD record
ord-ac29e85370a14115924b0911e8fc88d9
Source dataset
uspto-grants-2011_02
Patent number
US07893077B2

Reaction notes

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