Dimethylformamide → HCID 16065039, compound

HRID 1360696Notes

Reaction equation

HRID 1360696 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](O)=[O:24])=[CH:21][C:20]=1[F:29])[C:13](=[O:30])[CH:12]=[CH:11]2.[C:31](Cl)(=O)[C:32](Cl)=O.CN(C=O)C.[NH2:42][NH2:43]>C(Cl)Cl.C(OC)(OC)(OC)C.CO.C1(C)C=CC=CC=1>[F:29][C:20]1[CH:21]=[C:22]([C:23]2[O:24][C:31]([CH3:32])=[N:42][N:43]=2)[CH:26]=[C:27]([F:28])[C:19]=1[C:14]1[C:13](=[O:30])[CH:12]=[CH:11][N:10]2[C:15]=1[CH:16]=[CH:17][CH:18]=[C:9]2[C:3]1[CH:4]=[CH:5][C:6]([F:8])=[CH:7][C:2]=1[F:1]

Participants

9

Reactant 4

HCID 6228DimethylformamideHCID 9321HydrazineHCID 65578Oxalyl chlorideHCID 16064900HCID 16064900, compound

Product 1

HCID 16065039HCID 16065039, compound

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 1140TolueneSolventHCID 6344DichloromethaneSolvent2×HCID 15050Trimethyl orthoacetateSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 4-[6-(2,4-difluorophenyl)-2-oxo-2H-quinolizin-1-yl]-3,5-difluorobenzoic acid (Example 38, 204 mg, 0.49 mmol) in CH2Cl2 (1.5 mL) was added oxalyl chloride (93 mg, 0.74 mmol) and a catalytic amount of DMF at 0° C. After stirring at 0° C. for 5 min, the reaction was warmed to room temperature and stirred an additional for 30 min. The reaction was concentrated in vacuo and azeotrophed with toluene (2×). The crude material was dissolved in CH2Cl2 (1.5 mL) and was added to a solution of hydrazine (50 mmol) in CH2Cl2 (2 mL) at 0° C. After stirring for 15 min, the reaction was complete via LCMS analysis and the reaction was condensed to a solid, and azeotrophed with toluene (2×). The crude material was dissolved in trimethyl orthoacetate (5 mL) and methanol (2 mL) and heated to 120° C. for 1.5 hours. All volatile material was removed under reduced pressure and the crude material was purified via silica gel chromatography (100% EtOAc).

Workup

  1. customat 0° C
  2. temperaturethe reaction was warmed to room temperature
  3. stirringstirred an additional for 30 min
  4. concentrationThe reaction was concentrated in vacuo
  5. dissolutionThe crude material was dissolved in CH2Cl2 (1.5 mL)
  6. stirringAfter stirring for 15 min
  7. customcondensed to a solid
  8. customAll volatile material was removed under reduced pressure
  9. customthe crude material was purified via silica gel chromatography (100% EtOAc)

Sources & evidence

ORD record
ord-4c3453eea9f143ae97ac85dfbd9edee3
Source dataset
uspto-grants-2011_02
Patent number
US07879875B2

Reaction notes

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