Sulfuryl chloride → HCID 86687540, compound

HRID 1473486Notes

Reaction equation

HRID 1473486 reaction equation
[CH3:1][O:2][C:3]1[CH:15]=[CH:14][C:6]([CH2:7][NH:8][C:9]2[S:10][CH:11]=[CH:12][N:13]=2)=[CH:5][CH:4]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[Cl:26][C:27]1[C:36]2[C:31](=[CH:32][C:33]([S:38](Cl)(=[O:40])=[O:39])=[CH:34][C:35]=2[CH3:37])[N:30]=[CH:29][CH:28]=1.S(Cl)(Cl)(=O)=O>C1COCC1>[Cl:26][C:27]1[C:36]2[C:31](=[CH:32][C:33]([S:38]([N:8]([CH2:7][C:6]3[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:15][CH:14]=3)[C:9]3[S:10][CH:11]=[CH:12][N:13]=3)(=[O:39])=[O:40])=[CH:34][C:35]=2[CH3:37])[N:30]=[CH:29][CH:28]=1

Participants

6

Reactant 4

HCID 24648Sulfuryl chlorideHCID 578640N-[(4-methoxyphenyl)methyl]-1,3-thiazol-2-amineHCID 2733832Lithium HexamethyldisilazideHCID 86687541HCID 86687541, compound

Product 1

HCID 86687540HCID 86687540, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a flask containing ice cold suspension of N-(4-methoxybenzyl)thiazol-2-amine (25.1 mg, 0.114 mmol) in THF (418 μl) was added lithium bis(trimethylsilyl)amide (1M in THF) (120 μl, 0.120 mmol) dropwise over 10 min. The mixture was stirred for 15 min prior to the drop wise addition of a solution of 4-chloro-5-methylquinoline-7-sulfonyl chloride (30 mg, 0.109 mmol) in THF (0.6 ml). After 30 min LC/MS indicated desired product and methanolysis of the sulfonyl chloride (about 1:1). Additional solid N-(4-methoxybenzyl)thiazol-2-amine (25.1 mg, 0.114 mmol) was added with stirring at room temperature. After 15 min, no further conversion had occurred. Additional LHMDS (0.5 eq) was added after cooling back to 0° C. and stirring continued. After 20 min, LC/MS indicated consumption of sulfonyl chloride (methanolysis) with product visible as a minor species. To the orange/brown solution was added acetic acid (300 μl) and the mixture dried under reduced pressure. The crude material was purified with a 25 g (25 μm spherical) silica column ramping EtOAc in heptane (0-50%, 5% DCM throughout) to provide 4-chloro-N-(4-methoxybenzyl)-5-methyl-N-(thiazol-2-yl)quinoline-7-sulfonamide (6 mg, 0.013 mmol, 12.01% yield) as a white solid. m/z (ESI) 460.3 (M+H)+.

Workup

  1. additionTo a flask containing
  2. waitAfter 30 min LC/MS indicated

Sources & evidence

ORD record
ord-9912bef19cd5460b8617b2d6937e0a33
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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