Trimethylsilyldiazomethane → 5-Chloro-3-(2-fluoro-4-trimethylsilanyl-phenylamino)-pyrazine-2-carboxylic acid methyl ester

HRID 1500701Notes

Reaction equation

HRID 1500701 reaction equation
[Cl:1][C:2]1[N:3]=[C:4]([NH:11][C:12]2[CH:17]=[CH:16][C:15]([Si:18]([CH3:21])([CH3:20])[CH3:19])=[CH:14][C:13]=2[F:22])[C:5]([C:8]([OH:10])=[O:9])=[N:6][CH:7]=1.[CH3:23][Si](C=[N+]=[N-])(C)C>CO.C1(C)C=CC=CC=1.C(OCC)(=O)C>[CH3:23][O:9][C:8]([C:5]1[C:4]([NH:11][C:12]2[CH:17]=[CH:16][C:15]([Si:18]([CH3:19])([CH3:21])[CH3:20])=[CH:14][C:13]=2[F:22])=[N:3][C:2]([Cl:1])=[CH:7][N:6]=1)=[O:10]

Participants

6

Reactant 2

HCID 167693TrimethylsilyldiazomethaneHCID 591401225-Chloro-3-(2-fluoro-4-trimethylsilanyl-phenylamino)-pyrazine-2-carboxylic acid

Product 1

HCID 591401805-Chloro-3-(2-fluoro-4-trimethylsilanyl-phenylamino)-pyrazine-2-carboxylic acid methyl esterYield 71.1%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 5-chloro-3-(2-fluoro-4-trimethylsilanyl-phenylamino)-pyrazine-2-carboxylic acid (2.95 g, 8.68 mmol) in methanol (50 mL) and toluene (100 mL) at 0° C. under N2 was added a solution of 2M trimethylsilyldiazomethane in hexanes (9.55 mL, 19.0 mmol, 2.2 eq.), and the reaction mixture was stirred at ambient temperature for 30 minutes. The reaction mixture was diluted with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium bicarbonate, water and brine, then dried (Na2SO4), filtered and evaporated in vacuo. The resultant residue was purified by column chromotagraphy (Si-PPC, gradient 0 to 50% ethyl acetate in hexane) to give the desired compound as a yellow solid (2.18 g, 71.1%). 1H NMR (CDCl3, 400 MHz) δ ppm 10.54 (s, 1H), 8.36 (t, J=7.86 Hz, 1H), 8.06 (s, 1H), 7.34-7.26 (m, 2H), 4.05 (s, 3H), 0.28 (s, 9H); LCMS (method D1) RT=1.38 min, [M+H]+=354.

Workup

  1. washThe organic layer was washed with a saturated aqueous solution of sodium bicarbonate, water and brine
  2. dry with materialdried (Na2SO4)
  3. filtrationfiltered
  4. customevaporated in vacuo
  5. customThe resultant residue was purified by column chromotagraphy (Si-PPC, gradient 0 to 50% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-fe4c3d728ea445708710d16a16f1c223
Source dataset
uspto-grants-2015_12
Patent number
US09206174B2

Reaction notes

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