Water → HCID 18663188, compound

HRID 1956967Notes

Reaction equation

HRID 1956967 reaction equation
[CH3:1][C:2]1[C:3]([N:8](COCCOC)[S:9]([C:12]2[C:13]([C:18]3[CH:23]=[CH:22][C:21]([C:24]4[N:29]=[CH:28][CH:27]=[CH:26][N:25]=4)=[CH:20][C:19]=3[CH2:30][N:31]3[CH2:35][CH2:34][C:33]([CH3:37])([CH3:36])[C:32]3=[O:38])=[CH:14][CH:15]=[CH:16][CH:17]=2)(=[O:11])=[O:10])=[N:4][O:5][C:6]=1[CH3:7].C[Si](Cl)(C)C.[Na+].[I-].O>CC#N.CCOC(C)=O>[CH3:1][C:2]1[C:3]([NH:8][S:9]([C:12]2[C:13]([C:18]3[CH:23]=[CH:22][C:21]([C:24]4[N:29]=[CH:28][CH:27]=[CH:26][N:25]=4)=[CH:20][C:19]=3[CH2:30][N:31]3[CH2:35][CH2:34][C:33]([CH3:36])([CH3:37])[C:32]3=[O:38])=[CH:14][CH:15]=[CH:16][CH:17]=2)(=[O:11])=[O:10])=[N:4][O:5][C:6]=1[CH3:7]

Participants

7

Reactant 4

HCID 962WaterHCID 5238Sodium Iodide2×HCID 6397Chlorotrimethylsilane2×HCID 18663197HCID 18663197, compound

Product 1

HCID 18663188HCID 18663188, compound

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

To the solution of N-(4,5-dimethyl-3-isoxazolyl)-2'-[(3,3-dimethyl-2-oxo-1-pyrrolidinyl)methyl]-N-[(2-methoxyethoxy)methyl]-4'-(2-pyrimidinyl)[1,1'-biphenyl]-2-sulfonamide in 5.1 ml of CH3CN, trimethylsilyl chloride ("Me3SiCl", 166 mg, 1.53 mmol) was added, followed by NaI (229 mg, 1.53 mmol). The mixture was stirred at room temperature for 1 hr. Additional Me3SiCl (166 mg, 1.53 mmol) and NaI (229 mg, 1.53 mmol) were added in three portions and the reaction was stirred for an additional 1 hr and 20 minutes. The reaction mixture was then added to 5 ml H2O and 30 ml EtOAc. The organic layer was separated and washed with 2 ml saturated aqueous sodium thiosulfate, brine, dried and concentrated. The residue was purified by preparative HPLC on an ODS S10 column using 32% solvent A (10% MeOH, 90% H2O, 0.1% TFA) and 68% solvent B (90% MeOH, 10% H2O, 0.1% TFA) to provide the title compound of this Example (29 mg, 21% for two steps) as a white solid, m.p. 125°-132° C. (amorphous).

Workup

  1. stirringthe reaction was stirred for an additional 1 hr and 20 minutes
  2. customThe organic layer was separated
  3. washwashed with 2 ml saturated aqueous sodium thiosulfate, brine
  4. customdried
  5. concentrationconcentrated
  6. customThe residue was purified by preparative HPLC on an ODS S10 column

Sources & evidence

ORD record
ord-a4ffb38729394678b243f8d2ce5e2402
Source dataset
uspto-grants-1998_07
Patent number
US05780473

Reaction notes

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