Hydrazine → HCID 16064897, compound

HRID 1360687Notes

Reaction equation

HRID 1360687 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([CH:25]=[CH:26][C:27]=1[F:28])C(O)=O)[C:13](=[O:29])[CH:12]=[CH:11]2.C(Cl)(=O)C(Cl)=O.[NH2:36][NH2:37].[CH:38]([O:45][CH2:46][CH3:47])(OCC)OCC>C(Cl)Cl.CO.CN(C=O)C>[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:47]([C:46]3[O:45][CH:38]=[N:36][N:37]=3)[CH:25]=[CH:26][C:27]=1[F:28])[C:13](=[O:29])[CH:12]=[CH:11]2

Participants

8

Reactant 4

HCID 9321HydrazineHCID 31214Ethyl orthoformateHCID 65578Oxalyl chlorideHCID 16064758HCID 16064758, compound

Product 1

HCID 16064897HCID 16064897, compound

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 3-[6-(2,4-difluorophenyl)-2-oxo-2H-quinolizin-1-yl]-4-fluorobenzoic acid (Example 31, 400 mg, 1.01 μmol) in CH2Cl2 (5 mL) was added oxalyl chloride (190 mg, 1.50 mmol), and a catalytic amount of DMF at 0° C. After 15 minutes at 0° C. the ice bath was removed and the reaction warmed to ambient temperature. LCMS revealed the reaction was complete and all volatile material was removed in vacuo. The crude residue was dissolved in CH2Cl2 and was added to a hydrazine solution (10.1 mmol of hydrazine in 3 mL CH2Cl2) via cannula. After stirring for 10 min, the reaction was concentrated in vacuo to yield a solid. The crude material was dissolved in MeOH (1 mL) and triethyl orthoformate (4 mL) and heated to 120° C. for 1.5 hours. 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 (46 mg).

Workup

  1. customat 0° C
  2. customAfter 15 minutes at 0° C. the ice bath was removed
  3. customall volatile material was removed in vacuo
  4. dissolutionThe crude residue was dissolved in CH2Cl2
  5. concentrationthe reaction was concentrated in vacuo
  6. customto yield a solid
  7. concentrationthe mixture was concentrated in vacuo
  8. customThe crude material was purified via silica gel chromatography (CH2Cl2/EtOAc/MeOH)

Sources & evidence

ORD record
ord-c4c76010df3140abb10bd1b6153033b5
Source dataset
uspto-grants-2011_02
Patent number
US07879875B2

Reaction notes

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