Benzenesulfonamide → HCID 22660778, compound

HRID 392976Notes

Reaction equation

HRID 392976 reaction equation
[H-].[Na+].[C:3]1([S:9]([NH2:12])(=[O:11])=[O:10])[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[CH2:13]([O:20][C:21]1[CH:26]=[CH:25][C:24]([C:27]2[N:31]([CH:32]3[CH2:37][CH2:36][CH2:35][CH2:34][CH2:33]3)[C:30]3[CH:38]=[CH:39][C:40]([C:42](O)=[O:43])=[CH:41][C:29]=3[N:28]=2)=[CH:23][CH:22]=1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1>CN(C)C=O.ClCCl>[CH2:13]([O:20][C:21]1[CH:22]=[CH:23][C:24]([C:27]2[N:31]([CH:32]3[CH2:33][CH2:34][CH2:35][CH2:36][CH2:37]3)[C:30]3[CH:38]=[CH:39][C:40]([C:42]([C:4]4[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=4[S:9]([NH2:12])(=[O:11])=[O:10])=[O:43])=[CH:41][C:29]=3[N:28]=2)=[CH:25][CH:26]=1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1

Participants

6

Reactant 3

HCID 7370BenzenesulfonamideHCID 24758Sodium hydrideHCID 491098HCID 491098, compound

Product 1

HCID 22660778HCID 22660778, compoundYield 54%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Procedure

A suspension of compound 49 (0.060 g, 0.14 mmol) and thionyl chloride (0.051 mL) in benzene (2 mL) was refluxed for 2 h under an argon atmosphere. The reaction mixture was cooled to rt and concentrated on a rotary evaporator. The residue was coevaporated with benzene (2×) to afford the acid chloride as a white solid (0.062 g, 100%). Sodium hydride (0.0101 g, 0.252 mmol, 60% dispersion in oil was added to a solution of phenylsulfonamide (0.0425 g, 0.270 mmol) in dimethylformamide (1 mL) at rt under an argon atmosphere. After 1 h, dichloromethane was added (1 mL), followed by the acid chloride of 49 at 0° C. The reaction was warmed to rt. After 1 h, the reaction was diluted with dichloromethane and quenched with 1 N hydrochloric acid. The aqueous layer was washed with dichloromethane (3×). The combined organic layers were dried (MgSO4) and concentrated on a rotary evaporator. The residue was purified by column chromatography (silica gel, 25% acetone/toluene (v/v)). This material was further purified by reverse phase HPLC (C18 column, water/acetonitrile gradient containing 0.05% trifluoroacetic acid) to afford 55 as a white solid (0.0219 g, 54%). 1H NMR (CDCl3) δ 8.71 (d, 1H, J=1.1 Hz), 8.05 (m, 3H), 7.82 (d, 1H, J=8.8 Hz), 7.69 (d, 2H, J=9.1 Hz), 7.58 (m, 1H), 7.51-7.36 (m, 7H), 7.21 (d, 2H, 8.8 Hz), 5.16 (s, 2H), 4.52 (m, 1H), 2.32 (br m, 2H), 2.01 (br m, 4H), 1.80 (br m, 1H), 1.35 (br m, 3H); ESI-MS m/e 566.4 (M+1); HPLC purity (ELSD)>95%.

Workup

  1. waitAfter 1 h
  2. customquenched with 1 N hydrochloric acid
  3. washThe aqueous layer was washed with dichloromethane (3×)
  4. dry with materialThe combined organic layers were dried (MgSO4)
  5. concentrationconcentrated on a rotary evaporator
  6. customThe residue was purified by column chromatography (silica gel, 25% acetone/toluene (v/v))
  7. customThis material was further purified by reverse phase HPLC (C18 column, water/acetonitrile gradient containing 0.05% trifluoroacetic acid)

Sources & evidence

ORD record
ord-7d4e0df4f18c4a33856fe1d078e4db2e
Source dataset
uspto-grants-2004_10
Patent number
US06803374B2

Reaction notes

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