Lithium Hexamethyldisilazide → 2-(4-bromo-2-fluorophenylamino)-N-(2-hydroxyethoxy)-1,5-dimethyl-6-oxo-1,6-dihydropyridine-3-carboxamide

HRID 422823Notes

Reaction equation

HRID 422823 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[N:10]([CH3:26])[C:11](=[O:25])[C:12]([CH3:24])=[CH:13][C:14]=2[C:15]([NH:17][O:18][CH2:19][CH2:20][O:21]C=C)=[O:16])=[C:4]([F:27])[CH:3]=1.BrC1C=CC(NC2N(C)C(=O)C(C)=CC=2C(OC)=O)=C(F)C=1.C(OCCON)=C.C[Si]([N-][Si](C)(C)C)(C)C.[Li+]>C1COCC1>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[N:10]([CH3:26])[C:11](=[O:25])[C:12]([CH3:24])=[CH:13][C:14]=2[C:15]([NH:17][O:18][CH2:19][CH2:20][OH:21])=[O:16])=[C:4]([F:27])[CH:3]=1

Participants

6

Reactant 4

HCID 2733832Lithium HexamethyldisilazideHCID 21867017O-(2-(Vinyloxy)ethyl)hydroxylamineHCID 57636894Methyl 2-(4-bromo-2-fluorophenylamino)-1,5-dimethyl-6-oxo-1,6-dihydropyridine-3-carboxylateHCID 866246672-(4-bromo-2-fluorophenylamino)-1,5-dimethyl-6-oxo-N-(2-(vinyloxy)ethoxy)-1,6-dihydropyridine-3-carboxamide

Product 1

HCID 576369252-(4-bromo-2-fluorophenylamino)-N-(2-hydroxyethoxy)-1,5-dimethyl-6-oxo-1,6-dihydropyridine-3-carboxamideYield 94%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

Preparation of 2-(4-bromo-2-fluorophenylamino)-1,5-dimethyl-6-oxo-N-(2-(vinyloxy)ethoxy)-1,6-dihydropyridine-3-carboxamide: To a solution of methyl 2-(4-bromo-2-fluorophenylamino)-1,5-dimethyl-6-oxo-1,6-dihydropyridine-3-carboxylate (0.060 g, 0.16 mmol) in THF (2mL) was added O-(2-vinyloxy-ethyl)-hydroxylamine (0.042 ml, 0.41 mmol). The solution was cooled to 0° C. and lithium bis(trimethylsilyl)amide (0.81 ml, 0.81 mmol, 1 M solution in hexanes) was added dropwise. The reaction mixture was warmed to room temperature. After stirring for 35 minutes the reaction mixture was quenched by the addition of saturated NaHCO3 and partitioned between EtOAc and saturated NaCl. The layers were separated and the organic layer was dried (Na2SO4) and concentrated under reduced pressure. Purification by flash column chromatography (methylene chloride/MeOH, 20:1) gave 0.067 g (94%) pure desired product as an off-white crystalline solid.

Workup

  1. temperatureThe reaction mixture was warmed to room temperature
  2. customwas quenched by the addition of saturated NaHCO3
  3. custompartitioned between EtOAc and saturated NaCl
  4. customThe layers were separated
  5. dry with materialthe organic layer was dried (Na2SO4)
  6. concentrationconcentrated under reduced pressure
  7. customPurification by flash column chromatography (methylene chloride/MeOH, 20:1)

Sources & evidence

ORD record
ord-57b32c2a2f004ac09e299116e59204f6
Source dataset
uspto-grants-2012_01
Patent number
US08101639B2

Reaction notes

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