Lithium Hexamethyldisilazide → 6-Chloro-2-(4-(1,4-dimethylpiperidin-4-yl)phenylamino)-5-fluoronicotinamide

HRID 2044107Notes

Reaction equation

HRID 2044107 reaction equation
Cl[C:2]1[N:10]=[C:9]([Cl:11])[C:8]([F:12])=[CH:7][C:3]=1[C:4]([NH2:6])=[O:5].[CH3:13][N:14]1[CH2:19][CH2:18][C:17]([C:21]2[CH:27]=[CH:26][C:24]([NH2:25])=[CH:23][CH:22]=2)([CH3:20])[CH2:16][CH2:15]1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+]>C1COCC1>[Cl:11][C:9]1[C:8]([F:12])=[CH:7][C:3]([C:4]([NH2:6])=[O:5])=[C:2]([NH:25][C:24]2[CH:26]=[CH:27][C:21]([C:17]3([CH3:20])[CH2:16][CH2:15][N:14]([CH3:13])[CH2:19][CH2:18]3)=[CH:22][CH:23]=2)[N:10]=1

Participants

5

Reactant 3

HCID 2733832Lithium HexamethyldisilazideHCID 27740222,6-Dichloro-5-fluoronicotinamideHCID 574896554-(1,4-Dimethylpiperidin-4-yl)aniline

Product 1

HCID 574896566-Chloro-2-(4-(1,4-dimethylpiperidin-4-yl)phenylamino)-5-fluoronicotinamideYield 46.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 2,6-dichloro-5-fluoronicotinamide (287 mg, 1.372 mmol) and 4-(1,4-dimethylpiperidin-4-yl)aniline (267 mg, 1.307 mmol) in THF (10 mL) was added lithium bis(trimethylsilyl)amide (4.57 mL, 4.57 mmol) at room temperature. After 30 min, the reaction was quenched by the addition of satd. NH4Cl. The mixture was extracted with methylene chloride twice, the combined organic layers were washed with water and brine, and then concentrated. The residue was purified by MPLC (ISCO, 6-10% ammonia/methanol/methylene chloride, 40 g silica gel column) to give 229 mg of product as yellow solid.

Workup

  1. customthe reaction was quenched by the addition of satd
  2. extractionThe mixture was extracted with methylene chloride twice
  3. washthe combined organic layers were washed with water and brine
  4. concentrationconcentrated
  5. customThe residue was purified by MPLC (ISCO, 6-10% ammonia/methanol/methylene chloride, 40 g silica gel column)

Sources & evidence

ORD record
ord-e096b4d966394ff9acb40a7306612416
Source dataset
uspto-grants-2013_11
Patent number
US08586751B2

Reaction notes

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