Lithium Hexamethyldisilazide → HCID 86687709, compound

HRID 1473639Notes

Reaction equation

HRID 1473639 reaction equation
[CH3:1][O:2][C:3]1[CH:15]=[CH:14][C:6]([CH2:7][NH:8][C:9]2[N:10]=[CH:11][S:12][CH:13]=2)=[CH:5][CH:4]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].F[C:27]1[C:36]2[C:31](=[C:32](F)[C:33](F)=[C:34]([S:38]([O-])(=[O:40])=[O:39])[C:35]=2F)[C:30]([Cl:44])=[N:29][C:28]=1C1C(F)=C(F)C(F)=C(F)C=1F>C1COCC1>[Cl:44][C:30]1[C:31]2[C:36](=[CH:35][C:34]([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[N:10]=[CH:11][S:12][CH:13]=3)(=[O:40])=[O:39])=[CH:33][CH:32]=2)[CH:27]=[CH:28][N:29]=1

Participants

5

Reactant 3

HCID 2733832Lithium HexamethyldisilazideHCID 86687708N-(4-Methoxybenzyl)thiazol-4-amineHCID 86687710HCID 86687710, compound

Product 1

HCID 86687709HCID 86687709, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a flask containing ice cold suspension of N-(4-methoxybenzyl)thiazol-4-amine (Intermediate PPPPP; 0.085 g, 0.384 mmol) in THF (1.408 ml) was added lithium bis(trimethylsilyl)amide (0.403 ml, 0.403 mmol) drop wise over 10 min. The mixture was stirred for 15 minutes prior to the addition of a solution of perfluorophenyl-1-chloroisoquinoline-6-sulfonate (From Step 1 in Example 73; 0.15 g, 0.366 mmol) in THF (1.0 ml). After 45 minutes of stirring (ice melt) LCMS indicated that the reaction was nearly complete. The mixture was allowed to stir and slowly warm to room temperature overnight. LCMS indicated that the reaction was complete. The reaction was quenched by the addition of acetic acid (˜2 ml) and the resulting mixture was dried under reduced pressure and purified via silica gel chromatography (40 g silicycle HP column) ramping EtOAc in heptane (0-50%) providing product 1-chloro-N-(4-methoxybenzyl)-N-(thiazol-4-yl)isoquinoline-6-sulfonamide. m/z (ESI) 446.1 (M+H)+.

Workup

  1. additionTo a flask containing
  2. stirringAfter 45 minutes of stirring (ice melt) LCMS
  3. stirringto stir
  4. customThe reaction was quenched by the addition of acetic acid (˜2 ml)
  5. customthe resulting mixture was dried under reduced pressure
  6. custompurified via silica gel chromatography (40 g silicycle HP column)

Sources & evidence

ORD record
ord-e384ac51022742b7bc2493244a53f027
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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