Dimethylformamide → 6-Chloro-2-(2-fluoro-4-trimethylsilanyl-phenylamino)-nicotinic acid methyl ester

HRID 1500667Notes

Reaction equation

HRID 1500667 reaction equation
[Cl:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[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])[N:3]=1.[CH3:23]CN(C(C)C)C(C)C.CN(C=O)C.C(Cl)(=O)C(Cl)=O>ClCCl.CO>[CH3:23][O:7][C:6](=[O:8])[C:5]1[CH:9]=[CH:10][C:2]([Cl:1])=[N:3][C:4]=1[NH:11][C:12]1[CH:17]=[CH:16][C:15]([Si:18]([CH3:19])([CH3:21])[CH3:20])=[CH:14][C:13]=1[F:22]

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 81531Diisopropylethylamine2×HCID 591401476-Chloro-2-(2-fluoro-4-trimethylsilanyl-phenylamino)nicotinic acid

Product 1

HCID 591401556-Chloro-2-(2-fluoro-4-trimethylsilanyl-phenylamino)-nicotinic acid methyl ester

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

To a suspension of 6-chloro-2-(2-fluoro-4-trimethylsilanyl-phenylamino)-nicotinic acid (33.7 g, 99.5 mmol) in dichloromethane (500 mL) at 0° C. was added DIPEA (17.1 mL, 99.5 mmol). The reaction mixture was stirred for 10 minutes, then DMF (2 mL) and oxalyl chloride (8.7 mL, 99.5 mmol) were added dropwise (CAUTION: EFFERVESCENCE). The reaction mixture was stirred at room temperature for 2 hours and then added dropwise to a solution of DIPEA (17.1 mL, 99.5 mmol) in MeOH (500 mL) at 0° C. over a 45 minutes period. The reaction mixture was stirred at room temperature for 18 hours before being concentrated in vacuo. The resultant residue was dissolved in ethyl acetate and washed with a saturated aqueous solution of sodium hydrogen carbonate, followed by water, then brine, dried (Na2SO4), filtered and evaporated in vacuo to afford the title compound as a brown foam which was used without purification into the next step (36.4 g). LCMS (method B) RT=5.35 min, M+H+=353.

Workup

  1. stirringThe reaction mixture was stirred at room temperature for 2 hours
  2. stirringThe reaction mixture was stirred at room temperature for 18 hours
  3. concentrationbefore being concentrated in vacuo
  4. dissolutionThe resultant residue was dissolved in ethyl acetate
  5. washwashed with a saturated aqueous solution of sodium hydrogen carbonate
  6. dry with materialbrine, dried (Na2SO4)
  7. filtrationfiltered
  8. customevaporated in vacuo

Sources & evidence

ORD record
ord-e4a3d09992f147b9ab512b72d24a0b46
Source dataset
uspto-grants-2015_12
Patent number
US09206174B2

Reaction notes

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