2-Amino-6-chloro-N-methoxy-N-methyl-nicotinamide → (2-Amino-6-chloro-pyridin-3-yl)-(2-fluoro-phenyl)-methanone

HRID 30105

Reaction equation

HRID 30105 reaction equation
[NH2:1][C:2]1[N:13]=[C:12]([Cl:14])[CH:11]=[CH:10][C:3]=1[C:4](N(OC)C)=[O:5].[F:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1[Li]>O1CCCC1>[NH2:1][C:2]1[C:3]([C:4]([C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][C:16]=2[F:15])=[O:5])=[CH:10][CH:11]=[C:12]([Cl:14])[N:13]=1

Participants

4

Reactant 2

HCID 585908242-Amino-6-chloro-N-methoxy-N-methyl-nicotinamideHCID 178506686HCID 178506686, compound

Product 1

HCID 58590830(2-Amino-6-chloro-pyridin-3-yl)-(2-fluoro-phenyl)-methanoneYield 77%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

2-Amino-6-chloro-N-methoxy-N-methyl-nicotinamide (500 mg, 2.32 mmol, Example 3) was dissolved in anhydrous tetrahydrofuran (14 mL) and cooled to −78° C. A solution of 2-fluorophenyl lithium (4-6 equiv, freshly prepared following the same procedure as in Example 4) was added. The reaction was stirred at −78° C. for 1-3 hrs and quenched with aqueous ammonium chloride solution. The resulting mixture was extracted with ethyl acetate, washed with saturated sodium chloride, dried over sodium sulfate and evaporated in vacuo. The product was then purified on silica gel to give (2-Amino-6-chloro-pyridin-3-yl)-(2-fluoro-phenyl)-methanone as a white solid (445.5 mg, 77% yield). HRMS, observed: 250.0306, Calcd for M+: 250.0309.

Workup

  1. additionwas added
  2. customquenched with aqueous ammonium chloride solution
  3. extractionThe resulting mixture was extracted with ethyl acetate
  4. washwashed with saturated sodium chloride
  5. dry with materialdried over sodium sulfate
  6. customevaporated in vacuo
  7. customThe product was then purified on silica gel

Sources & evidence

ORD record
ord-eaad9f2e5822467f90ef726934124adc
Source dataset
uspto-grants-2008_09
Patent number
US07423051B2

Linked notes

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