Triethylamine → HCID 68547660, compound

HRID 1182181Notes

Reaction equation

HRID 1182181 reaction equation
[Br:1][C:2]1[CH:6]=[C:5]([C:7]([OH:9])=O)[N:4]([C:10]2[C:15]([Cl:16])=[CH:14][CH:13]=[CH:12][N:11]=2)[N:3]=1.[C:17](Cl)(=[O:21])[C:18](Cl)=O.C([N:25]([CH2:28][CH3:29])CC)C>ClCCl.C(N(CC)C=O)C.C(OCC)(=O)C.O>[Br:1][C:2]1[CH:6]=[C:5]([C:7]([NH:25][C:28]2[C:29]([C:17](=[O:21])[CH2:18][CH:5]([CH3:7])[CH3:6])=[CH:12][CH:13]=[CH:14][C:15]=2[CH3:10])=[O:9])[N:4]([C:10]2[C:15]([Cl:16])=[CH:14][CH:13]=[CH:12][N:11]=2)[N:3]=1

Participants

8

Reactant 3

HCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 115875353-Bromo-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxylic acid2×

Product 1

HCID 68547660HCID 68547660, compound

Reagents, catalysts & solvents 4

HCID 12051DiethylformamideCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
23 °C

Procedure

To a solution of 3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxylic acid (i.e. the pyrazole product of Step D) (500 mg, 1.65 mmol) in dichloromethane (10 mL) was added 1 drop of N,N-diethylformamide. Oxalyl Chloride (0.43 mL, 5 mmol) was added and the mixture was stirred at 23° C. for 1 hour. The solvent was removed under reduced pressure and the residue was diluted with acetonitrile (20 mL) and the solvent was again removed under reduced pressure. The residue was dissolved in tetrahydrofuran (10 mL) and treated with 1-(2-amino-3-methylphenyl)-3-methyl-1-butanone, prepared according to Chem. Pharm. Bull., 2000, 48, 1–15, (330 mg, 1.6 mmol) and finally triethylamine (0.45 mL, 3.2 mmol). The mixture was heated at 60° C. for 1 hour. The cooled reaction mixture was diluted with ethyl acetate (50 mL) and water (50 mL). The organic layer was washed with water (2×30 mL) and 1N hydrochloric acid (2×30 mL). The separated organic layer was dried over magnesium sulfate and evaporated to dryness under reduced pressure. The residue was subjected to silica gel chromatography using ethyl acetate/hexanes (3:7) as eluent. Appropriate fractions were pooled to afford, after removal of the solvents, the title compound, a compound of the invention (210 mg), as a yellow solid melting at 119–120° C. 1H NMR (CDCl3) δ 0.97 (d, 6H), 2.21 (s, 3H), 2.84 (d, 2H), 7.06 (s, 1H), 7.21 (m, 1H), 7.4 (m, 2H), 7.62 (d, 1H), 7.81 (d, 1H), 8.42 (d, 1H), 10.6 (br, 1H).

Workup

  1. customThe solvent was removed under reduced pressure
  2. additionthe residue was diluted with acetonitrile (20 mL)
  3. customthe solvent was again removed under reduced pressure
  4. dissolutionThe residue was dissolved in tetrahydrofuran (10 mL)
  5. additiontreated with 1-(2-amino-3-methylphenyl)-3-methyl-1-butanone
  6. customprepared
  7. temperatureThe mixture was heated at 60° C. for 1 hour
  8. customThe cooled reaction mixture
  9. washThe organic layer was washed with water (2×30 mL) and 1N hydrochloric acid (2×30 mL)
  10. dry with materialThe separated organic layer was dried over magnesium sulfate
  11. customevaporated to dryness under reduced pressure
  12. customto afford
  13. customafter removal of the solvents

Sources & evidence

ORD record
ord-96fb2ee674d948cfaf79ab34c7e39ba4
Source dataset
uspto-grants-2007_10
Patent number
US07288554B2

Reaction notes

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