Lithium Hexamethyldisilazide → 1-(4-chloro-2-methoxyphenyl)-N-(4-methoxybenzyl)-N-(pyrimidin-4-yl)phthalazine-6-sulfonamide

HRID 1473537Notes

Reaction equation

HRID 1473537 reaction equation
[CH3:1][O:2][C:3]1[CH:16]=[CH:15][C:6]([CH2:7][NH:8][C:9]2[CH:14]=[CH:13][N:12]=[CH:11][N:10]=2)=[CH:5][CH:4]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[Cl:27][C:28]1[CH:33]=[CH:32][C:31]([C:34]2[C:43]3[C:38](=[CH:39][C:40]([S:44](OC4C(F)=C(F)C(F)=C(F)C=4F)(=[O:46])=[O:45])=[CH:41][CH:42]=3)[CH:37]=[N:36][N:35]=2)=[C:30]([O:59][CH3:60])[CH:29]=1>C1COCC1.[Cl-].[NH4+].O>[Cl:27][C:28]1[CH:33]=[CH:32][C:31]([C:34]2[C:43]3[C:38](=[CH:39][C:40]([S:44]([N:8]([CH2:7][C:6]4[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:16][CH:15]=4)[C:9]4[CH:14]=[CH:13][N:12]=[CH:11][N:10]=4)(=[O:45])=[O:46])=[CH:41][CH:42]=3)[CH:37]=[N:36][N:35]=2)=[C:30]([O:59][CH3:60])[CH:29]=1

Participants

7

Reactant 3

HCID 2733832Lithium HexamethyldisilazideHCID 13230138N-(4-methoxybenzyl)pyrimidin-4-amineHCID 86687594Perfluorophenyl 1-(4-chloro-2-methoxyphenyl)phthalazine-6-sulfonate

Product 1

HCID 866875961-(4-chloro-2-methoxyphenyl)-N-(4-methoxybenzyl)-N-(pyrimidin-4-yl)phthalazine-6-sulfonamideYield 36.8%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×HCID 25517Ammonium ChlorideSolvent

Procedure

A round-bottom flask was charged with N-(4-methoxybenzyl)pyrimidin-4-amine (80 mg, 0.371 mmol) and THF (1238 μl) to give a clear solution. The flask was cooled in a dry ice-acetone bath for 5 min, then lithium bis(trimethylsilyl)amide (1M in THF) (371 μl, 0.371 mmol) was added drop wise. The flask was removed from the cooling bath for 3 min, and then re-cooled in the bath. A solution of perfluorophenyl 1-(4-chloro-2-methoxyphenyl)phthalazine-6-sulfonate (128 mg, 0.248 mmol) in THF (1 mL with a 0.5 mL-flask wash) was added drop wise. After another minute, the flask was transferred to an ice-water bath. After 5 min, the mixture was diluted with saturated aq. ammonium chloride and water, then extracted with EtOAc (2×). The combined organic extracts were dried over sodium sulfate, filtered, and concentrated. The residue was purified by chromatography on silica gel (12-g Redi-Sep Gold column, 50-100% EtOAc/Heptane) to give 1-(4-chloro-2-methoxyphenyl)-N-(4-methoxybenzyl)-N-(pyrimidin-4-yl)phthalazine-6-sulfonamide (50 mg, 0.091 mmol, 36.8% yield) as an off-white solid. m/z (ESI) 548.2 (M+H)+.

Workup

  1. customto give a clear solution
  2. temperatureThe flask was cooled in a dry ice-acetone bath for 5 min
  3. customThe flask was removed from the cooling bath for 3 min
  4. temperaturere-cooled in the bath
  5. additionwas added drop wise
  6. customAfter another minute, the flask was transferred to an ice-water bath
  7. extractionextracted with EtOAc (2×)
  8. dry with materialThe combined organic extracts were dried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe residue was purified by chromatography on silica gel (12-g Redi-Sep Gold column, 50-100% EtOAc/Heptane)

Sources & evidence

ORD record
ord-2485b91c0cbe44e4a6eb6a579323a832
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

Loading…