Triethylamine → HCID 16064896, compound

HRID 1360686Notes

Reaction equation

HRID 1360686 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[N:10]2[C:15]([CH:16]=[CH:17][CH:18]=1)=[C:14]([C:19]1[CH:20]=[C:21]([CH:25]=[CH:26][C:27]=1[F:28])[C:22](O)=[O:23])[C:13](=[O:29])[CH:12]=[CH:11]2.[CH2:30]([N:32](CC)CC)[CH3:31].C(OC(Cl)=O)C.[NH2:43]N>C(Cl)Cl>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[N:10]2[C:15]([CH:16]=[CH:17][CH:18]=1)=[C:14]([C:19]1[CH:20]=[C:21]([C:22]3[O:23][C:30]([CH3:31])=[N:32][N:43]=3)[CH:25]=[CH:26][C:27]=1[F:28])[C:13](=[O:29])[CH:12]=[CH:11]2

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 9321HydrazineHCID 10928Ethyl chloroformateHCID 16064758HCID 16064758, compound

Product 1

HCID 16064896HCID 16064896, compoundYield 41%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 3-[6-(2,4-difluorophenyl)-2-oxo-2H-quinolizin-1-yl]-4-fluorobenzoic acid (Example 31, 1.0 g, 2.53 mmol) in CH2Cl2 (20 mL) was added triethyl amine (511 mg, 5.06 mmol) and ethylchloroformate (409 mg, 3.79 mmol) at 0° C. The mixture was warmed to ambient temperature and allowed to stir for an additional 1 h. The reaction was quenched with aqueous NH4Cl, extracted with CH2Cl2 and washed with 0.5 N HCl (1×), brine, dried over MgSO4, and concentrated in vacou. The crude mixture was dissolved in CH2Cl2 and was added to a hydrazine solution (25.3 mmol of hydrazine in 10 mL CH2Cl2) via cannula. After stirring for 10 min at room temperature, the reaction was concentrated in vacuo to yield a solid. The crude solid was washed with MeOH and ether/EtOAc (1/1) to remove impurity. The resulting solid was added MeOH (5 mL) and trimethyl orthoacetate (20 mL) and heated to 110° C. for 2 hrs. LCMS revealed the reaction was complete and the mixture was concentrated in vacuo. The crude material was purified via silica gel chromatography (CH2Cl2/EtOAc/MeOH) to give the title compound as a yellowish solid (450 mg).

Workup

  1. customThe reaction was quenched with aqueous NH4Cl
  2. extractionextracted with CH2Cl2
  3. washwashed with 0.5 N HCl (1×), brine
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated in vacou
  6. dissolutionThe crude mixture was dissolved in CH2Cl2
  7. stirringAfter stirring for 10 min at room temperature
  8. concentrationthe reaction was concentrated in vacuo
  9. customto yield a solid
  10. washThe crude solid was washed with MeOH and ether/EtOAc (1/1)
  11. customto remove impurity
  12. additionThe resulting solid was added MeOH (5 mL) and trimethyl orthoacetate (20 mL)
  13. temperatureheated to 110° C. for 2 hrs
  14. concentrationthe mixture was concentrated in vacuo
  15. customThe crude material was purified via silica gel chromatography (CH2Cl2/EtOAc/MeOH)

Sources & evidence

ORD record
ord-c4ba2d9e2ded4839a4c6486cc22f6ff7
Source dataset
uspto-grants-2011_02
Patent number
US07879875B2

Reaction notes

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