Lithium Hexamethyldisilazide → 1-(1-Ethyl-propyl)-7-methyl-5-(2,4,6-trimethyl-phenoxy)-1,4-dihydro-2H-pyrido[3,4-b]pyrazin-3-one

HRID 2298427Notes

Reaction equation

HRID 2298427 reaction equation
Cl[CH2:2][C:3]([NH:5][C:6]1[C:7]([O:19][C:20]2[C:25]([CH3:26])=[CH:24][C:23]([CH3:27])=[CH:22][C:21]=2[CH3:28])=[N:8][C:9]([CH3:18])=[CH:10][C:11]=1[NH:12][CH:13]([CH2:16][CH3:17])[CH2:14][CH3:15])=[O:4].C[Si]([N-][Si](C)(C)C)(C)C.[Li+]>C1COCC1>[CH2:14]([CH:13]([N:12]1[CH2:2][C:3](=[O:4])[NH:5][C:6]2[C:7]([O:19][C:20]3[C:25]([CH3:26])=[CH:24][C:23]([CH3:27])=[CH:22][C:21]=3[CH3:28])=[N:8][C:9]([CH3:18])=[CH:10][C:11]1=2)[CH2:16][CH3:17])[CH3:15]

Participants

4

Reactant 2

HCID 2733832Lithium Hexamethyldisilazide2×HCID 120183492-Chloro-N-[4-(1-ethyl-propylamino)-6-methyl-2-(2,4,6-trimethyl-phenoxy)-pyridin-3-yl]-acetamide

Product 1

HCID 120183501-(1-Ethyl-propyl)-7-methyl-5-(2,4,6-trimethyl-phenoxy)-1,4-dihydro-2H-pyrido[3,4-b]pyrazin-3-oneYield 103.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 2-chloro-N-[4-(1-ethyl-propylamino)-6-methyl-2-(2,4,6-trimethyl-phenoxy)-pyridin-3-yl]-acetamide (170 mg, 0.42 mml) in 2 ml of dry THF was added a solution of 1 M lithium bis(trimethylsilyl)amide in THF (0.84 ml, 0.84 mmol) at −78° C. The mixture was gradually warmed to room temperature and stirred at room temperature for 2 hours. An additional 0.42 ml of 1M lithium bis(trimethylsilyl)amide in HF was added at −78° C. and the resulting mixture was stirred at room temperature overnight. The mixture was quenched with water and extracted with ethyl acetate. The organic layer was dried and concentrated to dryness to give 160 mg of yellow solid. The solid residue was purified through silica gel column chromatography using 15% ethyl acetate (EtOAc) in hexane as eluent to give 91 mg (59%) of the title compound as white crystals. 1H NMR (CDCl3) δ 7.84 (s, 1H), 6.88 (s,2H), 6.22 (s,1H), 3.82(s,2H), 3.58(m,1H), 2.30(s,3H), 2.18(s,3H), 2.08(s,6H), 1.63(m,4H), 0.95(m,6H) ppm.

Workup

  1. stirringthe resulting mixture was stirred at room temperature overnight
  2. customThe mixture was quenched with water
  3. extractionextracted with ethyl acetate
  4. customThe organic layer was dried
  5. concentrationconcentrated to dryness

Sources & evidence

ORD record
ord-fb03d40a14224d1dad230a59b9c57971
Source dataset
uspto-grants-2002_12
Patent number
US06492520B1

Reaction notes

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