Triethylamine → HCID 58138769, compound

HRID 1677721Notes

Reaction equation

HRID 1677721 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:16]3[CH:15]=[CH:14][CH:13]=[C:12]([C:17]([OH:19])=O)[C:11]=3[CH:10]=[N:9]2)=[CH:4][CH:3]=1.Cl.[Br:21][C:22]1[N:27]=[CH:26][C:25]([C@@H:28]([NH2:31])[CH2:29][CH3:30])=[CH:24][CH:23]=1.C(N(CC)CC)C>S(Cl)(Cl)=O.ClCCl.[Cl-].[NH4+]>[Br:21][C:22]1[N:27]=[CH:26][C:25]([C@@H:28]([NH:31][C:17]([C:12]2[C:11]3[CH:10]=[N:9][N:8]([C:5]4[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=4)[C:16]=3[CH:15]=[CH:14][CH:13]=2)=[O:19])[CH2:29][CH3:30])=[CH:24][CH:23]=1

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 581387741-(4-fluoro-phenyl)-1H-indazole-4-carboxylic acidHCID 86650869HCID 86650869, compound

Product 1

HCID 58138769HCID 58138769, compound

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 24386Thionyl ChlorideSolventHCID 25517Ammonium ChlorideSolvent

Procedure

A suspension of 1-(4-fluoro-phenyl)-1H-indazole-4-carboxylic acid (258 mg, 1.00 mmol) was heated at reflux in thionyl chloride (5 mL) until the solid dissolved. After 45 minutes, the mixture was concentrated to dryness. The yellow residue was diluted with dichloromethane and (S)-1-(6-bromo-pyridin-3-yl)-propylamine hydrochloride (288 mg, 1.00 mmol) was added followed by triethylamine (1.0 mL, 7.2 mmol). After 30 minutes, the reaction was diluted with saturated aqueous ammonium chloride (10 mL) and extracted with ethyl acetate (4×10 mL). The combined organic layers were washed with brine (3×10 mL), dried over magnesium sulfate, filtered and concentrated. The crude material was diluted with dichloromethane and purified by silica gel chromatography eluting with a gradient of 0-100% ethyl acetate in hexanes. The material from the column was triturated with ether to afford 1-(4-fluoro-phenyl)-1H-indazole-4-carboxylic acid [(S)-1-(6-bromo-pyridin-3-yl)-propyl]-amide.

Workup

  1. temperaturewas heated
  2. dissolutiondissolved
  3. concentrationthe mixture was concentrated to dryness
  4. additionwas added
  5. waitAfter 30 minutes
  6. extractionextracted with ethyl acetate (4×10 mL)
  7. washThe combined organic layers were washed with brine (3×10 mL)
  8. dry with materialdried over magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated
  11. additionThe crude material was diluted with dichloromethane
  12. custompurified by silica gel chromatography
  13. washeluting with a gradient of 0-100% ethyl acetate in hexanes
  14. customThe material from the column was triturated with ether

Sources & evidence

ORD record
ord-05e1f3e0df0f48769dcc09506587a36c
Source dataset
uspto-grants-2011_08
Patent number
US08008327B2

Reaction notes

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