Lithium Hexamethyldisilazide → HCID 90110410, compound

HRID 1051413Notes

Reaction equation

HRID 1051413 reaction equation
[CH3:1][O:2][C:3]1[CH:17]=[C:16]([O:18][CH3:19])[CH:15]=[CH:14][C:4]=1[CH2:5][NH:6][C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([F:13])[N:8]=1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[CH3:30][C:31]1[CH:39]=[C:38]2[C:34]([CH:35]=[N:36][NH:37]2)=[CH:33][C:32]=1[S:40](Cl)(=[O:42])=[O:41]>C1COCC1>[CH3:1][O:2][C:3]1[CH:17]=[C:16]([O:18][CH3:19])[CH:15]=[CH:14][C:4]=1[CH2:5][N:6]([C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([F:13])[N:8]=1)[S:40]([C:32]1[CH:33]=[C:34]2[C:38](=[CH:39][C:31]=1[CH3:30])[NH:37][N:36]=[CH:35]2)(=[O:42])=[O:41]

Participants

5

Reactant 3

HCID 2733832Lithium Hexamethyldisilazide2×HCID 55136848HCID 55136848, compoundHCID 90112225HCID 90112225, compound

Product 1

HCID 90110410HCID 90110410, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-78 °C

Procedure

Added N-(2,4-dimethoxybenzyl)-6-fluoropyridin-2-amine (1.0 g, 3.87 mmol) to THF (19 mL) and cooled to −78° C. Added LHMDS (6.5 mL, 6.45 mmol), warmed to RT, stirred for 30 min, and cooled back to −78° C. Following addition of LHMDS, solution turned clear and pink in color. After warming to RT, solution became clear, yellow. At −78° C., added 6-methyl-1H-indazole-5-sulfonyl chloride (4-4, 594.8 mg, 2.58 mmol) in THF (6.5 mL) at −78° C. via syringe followed by THF rinse. Solution remained yellow in color. Allowed reaction flask to remain in bath and gradually warm to RT overnight. Following this duration, quenched with 40 mL saturated NH4Cl, diluted with 20 mL EtOAc. Separated layers, back-extracted aqueous with 3×10 mL EtOAc. Dried organics over Na2SO4, filtered, concentrated to give an orange oil. Purified by normal-phase ISCO (40 g column, 0-50% EtOAc:Hex) to give 4-5 as a white solid.

Workup

  1. temperaturecooled back to −78° C
  2. temperatureAfter warming to RT
  3. washrinse
  4. customAllowed reaction flask to remain in bath
  5. temperaturegradually warm to RT overnight
  6. customquenched with 40 mL saturated NH4Cl
  7. additiondiluted with 20 mL EtOAc
  8. extractionSeparated layers, back-extracted aqueous with 3×10 mL EtOAc
  9. filtrationDried organics over Na2SO4, filtered
  10. concentrationconcentrated
  11. customto give an orange oil
  12. customPurified by normal-phase ISCO (40 g column, 0-50% EtOAc:Hex)

Sources & evidence

ORD record
ord-45b1a208120f481a859553ca494df4c6
Source dataset
uspto-grants-2016_07
Patent number
US09388179B2

Reaction notes

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