Hydrazine → HCID 16065040, compound

HRID 1360697Notes

Reaction equation

HRID 1360697 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[C:27]([F:28])=[CH:26][C:22]([C:23]([OH:25])=O)=[CH:21][C:20]=1[F:29])C(=O)C=[CH:11]2.[C:31](Cl)(=[O:35])[C:32](Cl)=O.[NH2:37][NH2:38].[N:39]#[C:40]Br>C(Cl)Cl.CO.CN(C=O)C>[NH2:39][C:40]1[O:25][C:23]([C:22]2[CH:21]=[C:20]([F:29])[C:19]([C:14]3[C:31](=[O:35])[CH:32]=[CH:11][N:10]4[C:15]=3[CH:16]=[CH:17][CH:18]=[C:9]4[C:3]3[CH:4]=[CH:5][C:6]([F:8])=[CH:7][C:2]=3[F:1])=[C:27]([F:28])[CH:26]=2)=[N:38][N:37]=1

Participants

8

Reactant 4

HCID 9321HydrazineHCID 10476Cyanogen BromideHCID 65578Oxalyl chlorideHCID 16064900HCID 16064900, compound

Product 1

HCID 16065040HCID 16065040, compoundYield 9.9%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 4-[6-(2,4-difluorophenyl)-2-oxo-2H-quinolizin-1-yl]-3,5-difluorobenzoic acid (Example 38, 50 mg, 0.12 mmol) in CH2Cl2 was added oxalyl chloride (22 mg, 0.18 mmol) and a catalytic amount of DMF at 0° C. After 10 min the reaction was removed from the ice bath and stirred at room temperature for 20 min. LCMS analysis revealed the reaction was complete and the reaction was concentrated in vacuo. To this crude reside in CH2Cl2 was added to a hydrazine solution (1.2 mmol hydrazine in 1 mL CH2Cl2) at 0° C. via cannula. After 10 min at 0° C. the reaction was allowed to warn to room temperature. The reaction was concentrated in vacuo to yield a solid which was added methanol (1 mL) and cyanogen bromide (126 mg, 1.2 mmol) and heated to 90° C. for 2 hrs. LCMS revealed the reaction was complete and the mixture was concentrated in vacuo. The crude material was purified via reverse phase chromatography to give the title compound (5.4 mg).

Workup

  1. customat 0° C
  2. customAfter 10 min the reaction was removed from the ice bath
  3. concentrationthe reaction was concentrated in vacuo
  4. waitAfter 10 min at 0° C. the reaction was allowed
  5. customto warn to room temperature
  6. concentrationThe reaction was concentrated in vacuo
  7. customto yield a solid which
  8. temperatureheated to 90° C. for 2 hrs
  9. concentrationthe mixture was concentrated in vacuo
  10. customThe crude material was purified via reverse phase chromatography

Sources & evidence

ORD record
ord-fedb15b51d314125899fa19c2912fb2a
Source dataset
uspto-grants-2011_02
Patent number
US07879875B2

Reaction notes

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