Methylamine → HCID 22176599, compound

HRID 1797216Notes

Reaction equation

HRID 1797216 reaction equation
C(Cl)(=O)C(Cl)=O.[F:7][C:8]([C:18]1[CH:23]=[CH:22][C:21]([NH:24][C:25]([C:27]2[N:32]=[CH:31][C:30]([C:33](O)=[O:34])=[CH:29][CH:28]=2)=[O:26])=[CH:20][CH:19]=1)([CH3:17])[CH2:9][NH:10][S:11]([CH:14]([CH3:16])[CH3:15])(=[O:13])=[O:12].O1CCOCC1.[CH3:42][NH2:43]>C(Cl)Cl.CN(C=O)C.O>[F:7][C:8]([C:18]1[CH:19]=[CH:20][C:21]([NH:24][C:25]([C:27]2[CH:28]=[CH:29][C:30]([C:33](=[O:34])[NH:43][CH3:42])=[CH:31][N:32]=2)=[O:26])=[CH:22][CH:23]=1)([CH3:17])[CH2:9][NH:10][S:11]([CH:14]([CH3:16])[CH3:15])(=[O:12])=[O:13]

Participants

8

Reactant 4

HCID 6329MethylamineHCID 312751,4-DioxaneHCID 65578Oxalyl chlorideHCID 22176530HCID 22176530, compound

Product 1

HCID 22176599HCID 22176599, compoundYield 25%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

Into a 50 mL single neck flask, 1 mL oxalyl chloride was added syringe wise to 6-{N-[4-(1-fluoro-1-methyl-2-{[(methylethyl)sulfonyl]amino}ethyl)phenyl]carbamoyl}pyridine-3-carboxylic acid. (110 mg, 0.26 mmol, prepared in example 51) in methylene chloride (10 mL) while stirring under nitrogen at room temperature. Immediately, 1 drop of DMF was added by pipette initiating a foaming of the mixture. The reaction was stirred one hour at this temperature and then concentrated under reduced vacuum to yield a white semi-solid. This material was placed into dioxane (10 mL) and added dropwise to a stirring solution of 40% methylamine in water (3 mL, excess) at room temperature and the mixture was stirred overnight. In the morning, the solution was concentrated under reduced vacuum and the resulting oil was taken into methylene chloride and the organic layer was washed once with H2O, dried over K2CO3, filtered, and concentrated under reduced vacuum to yield 78 mg as an oil. This material was purified via silica gel chromatography employing the chromatotron and using a 1000 micron rotor while eluting with a solvent of ethyl acetate to yield the title compound (28 mg, 25%) as a white solid. Ion spray M.S. 435.2 (M*−1) and 417.1 (M*−19 Fluorine).

Workup

  1. stirringThe reaction was stirred one hour at this temperature
  2. concentrationconcentrated under reduced vacuum
  3. customto yield a white semi-solid
  4. stirringthe mixture was stirred overnight
  5. concentrationIn the morning, the solution was concentrated under reduced vacuum
  6. washthe organic layer was washed once with H2O
  7. dry with materialdried over K2CO3
  8. filtrationfiltered
  9. concentrationconcentrated under reduced vacuum
  10. customto yield 78 mg as an oil
  11. customThis material was purified via silica gel chromatography
  12. washwhile eluting with a solvent of ethyl acetate

Sources & evidence

ORD record
ord-8aa9e5bad5a244a5afb3cb9304f3c7fb
Source dataset
uspto-grants-2006_04
Patent number
US07034045B1

Reaction notes

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