Potassium bis(trimethylsilyl)amide → HCID 21717276, compound

HRID 1386246Notes

Reaction equation

HRID 1386246 reaction equation
C[Si]([N-][Si](C)(C)C)(C)C.[K+].Cl[C:12]1[C:21]2[C:16](=[CH:17][C:18]([O:24][CH2:25][CH2:26][O:27][CH3:28])=[C:19]([O:22][CH3:23])[CH:20]=2)[N:15]=[CH:14][N:13]=1.[CH2:29]([O:31][CH:32]([O:43][CH2:44][CH3:45])[N:33]1[C:41]2[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=2)[CH2:35][C:34]1=[O:42])[CH3:30]>C1(C)C=CC=CC=1.C1COCC1>[CH2:44]([O:43][CH:32]([O:31][CH2:29][CH3:30])[N:33]1[C:41]2[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=2)[CH:35]([C:12]2[C:21]3[C:16](=[CH:17][C:18]([O:24][CH2:25][CH2:26][O:27][CH3:28])=[C:19]([O:22][CH3:23])[CH:20]=3)[N:15]=[CH:14][N:13]=2)[C:34]1=[O:42])[CH3:45]

Participants

6

Reactant 3

HCID 3251421Potassium bis(trimethylsilyl)amideHCID 107306534-Chloro-6-methoxy-7-(2-methoxyethoxy)quinazolineHCID 10879089HCID 10879089, compound

Product 1

HCID 21717276HCID 21717276, compoundYield 74%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Procedure

Potassium bis(trimethylsilyl)amide (48 ml of a 0.5M solution in toluene, 24 mmol) was rapidly added to a solution of 4-chloro-6-methoxy-7-(2-methoxyethoxy)quinazoline (3.2 g, 11.9 mmol) and 1-diethoxymethyloxindole (4.0 g, 14.9 mmol), (prepared according to Synthesis 1975, 168), in THF (240 ml) at ambient temperature. After 2 hours, the precipitate was filtered off and washed with ether. The filtrate was evaporated. The residue was mixed with the precipitate and partitioned between methylene chloride and water and the organic phase washed with saturated aqueous sodium chloride solution. The organic layer was driied (MgSO4) and the solvent removed by evaporation. The residue was purified by column flash chromatography using methylene chloride/methanol (95/5) as eluent. The purified product was triturated with a mixture of ether and petroleum ether to give 4-(1-diethoxymethyloxindol-3-yl)-6-methoxy-7-(2-methoxyethoxy)quinazoline (4.03 g, 74%) as a red orange solid.

Workup

  1. filtrationthe precipitate was filtered off
  2. washwashed with ether
  3. customThe filtrate was evaporated
  4. additionThe residue was mixed with the precipitate
  5. custompartitioned between methylene chloride and water
  6. washthe organic phase washed with saturated aqueous sodium chloride solution
  7. customthe solvent removed by evaporation
  8. customThe residue was purified by column flash chromatography
  9. customThe purified product was triturated with a mixture of ether and petroleum ether

Sources & evidence

ORD record
ord-234807c489ed44019889b4a51198fe1e
Source dataset
uspto-grants-2001_07
Patent number
US06265411B1

Reaction notes

Loading…