Triethylamine → HCID 57860549, compound

HRID 1947162Notes

Reaction equation

HRID 1947162 reaction equation
Cl[C:2]1[CH:7]=[CH:6][N:5]=[C:4]([C:8]([OH:10])=O)[CH:3]=1.Cl.CN.C1C=CC2N(O)N=[N:20][C:18]=2C=1.C(N(CC)CC)C.[CH3:31][O:32][C:33]1[C:37]2[C:38](=[O:55])[N:39]([CH2:46][C:47](=[O:54])[C:48]3[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=3)[C:40]3[CH:41]=[CH:42][CH:43]=[CH:44][C:45]=3[C:36]=2[N:35]([CH3:56])[C:34]=1[C:57]([NH:59][CH:60]1[CH2:65][CH2:64][NH:63][CH2:62][CH2:61]1)=[O:58].C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.C(=O)([O-])O.[Na+]>[CH3:31][O:32][C:33]1[C:37]2[C:38](=[O:55])[N:39]([CH2:46][C:47](=[O:54])[C:48]3[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=3)[C:40]3[CH:41]=[CH:42][CH:43]=[CH:44][C:45]=3[C:36]=2[N:35]([CH3:56])[C:34]=1[C:57]([NH:59][CH:60]1[CH2:61][CH2:62][N:63]([C:2]2[CH:7]=[CH:6][N:5]=[C:4]([C:8](=[O:10])[NH:20][CH3:18])[CH:3]=2)[CH2:64][CH2:65]1)=[O:58]

Participants

9

Reactant 6

HCID 8471Triethylamine2×HCID 11430Potassium CarbonateHCID 757711-HydroxybenzotriazoleHCID 2308904-Chloropyridine-2-carboxylic acidHCID 6364545Methylamine hydrochlorideHCID 57860479HCID 57860479, compound

Product 1

HCID 57860549HCID 57860549, compoundYield 11.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 516892Sodium BicarbonateSolvent2×

Procedure

To a solution of 4-chloropyridine-2-carboxylic acid (200 mg, 1.3 mmol), methylamine hydrochloride (103 mg, 1.5 mmol), HOBt (205 mg, 1.5 mmol) and triethylamine (0.42 mL, 3.0 mmol) in DMF (3.0 mL) was added WSCD (292 mg, 1.5 mmol) under ice-cooling, and the mixture was stirred at room temperature for 5 hr. The reaction mixture was diluted with saturated sodium hydrogen carbonate solution, and extracted twice with ethyl acetate. The extracts were combined, washed with brine, dried over magnesium sulfate, filtered through aminosilica gel, and the filtrate was concentrated under reduced pressure. The residue was dissolved in DMF (3.0 mL), the compound of Example 77 (300 mg, 0.59 mmol), potassium carbonate (204 mg, 1.5 mmol) and triethylamine (0.082 mL, 0.59 mmol) were added, and the mixture was stirred at 100° C. for 16 hr. The reaction mixture was diluted with saturated sodium hydrogen carbonate solution, and extracted twice with a mixed solvent of ethyl acetate-THF. The extract was dried over magnesium sulfate, and concentrated under reduced pressure. The residue was purified by aminosilica gel chromatography (eluate; ethyl acetate/hexane=40/60-100/0) and recrystallized from ethyl acetate-hexane to give the title compound (40 mg, 11%) as a pale-yellow solid.

Workup

  1. temperaturecooling
  2. extractionextracted twice with ethyl acetate
  3. washwashed with brine
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered through aminosilica gel
  6. concentrationthe filtrate was concentrated under reduced pressure
  7. dissolutionThe residue was dissolved in DMF (3.0 mL)
  8. stirringthe mixture was stirred at 100° C. for 16 hr
  9. extractionextracted twice with a mixed solvent of ethyl acetate-THF
  10. dry with materialThe extract was dried over magnesium sulfate
  11. concentrationconcentrated under reduced pressure
  12. customThe residue was purified by aminosilica gel chromatography (eluate; ethyl acetate/hexane=40/60-100/0)
  13. customrecrystallized from ethyl acetate-hexane

Sources & evidence

ORD record
ord-e4a6528109bb4f8e94834361838a9be3
Source dataset
uspto-grants-2013_03
Patent number
US08399449B2

Reaction notes

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