1,2-Dichloroethane → HCID 16065041, compound

HRID 1360698Notes

Reaction equation

HRID 1360698 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:13](=[O:30])[CH:12]=[CH:11]2.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.O[N:46]=[C:47]([NH2:49])[CH3:48]>CN1C(=O)CCC1>[F:29][C:20]1[CH:21]=[C:22]([C:23]2[O:25][N:49]=[C:47]([CH3:48])[N:46]=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

6

Reactant 4

HCID 111,2-DichloroethaneHCID 30926N-HydroxyacetamidineHCID 757711-HydroxybenzotriazoleHCID 16064900HCID 16064900, compound

Product 1

HCID 16065041HCID 16065041, compound

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
90 °C

Procedure

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 NMP (1.2 mL) was added EDC (46 mg, 0.24 mmol), and HOBT (24 mg, 0.18 mmol) at room temperature. The reaction was stirred at room temperature for 30 minutes before N′-hydroxyethanimidamide was added. The reaction was heated to 90° C. for 6 hours and yielded an 80% conversion of product via LCMS. The reaction was quenched with NH4Cl and extracted with EtOAc (3×). The combined organic layers were washed with 0.5 N HCl, water, brine, dried over MgSO4, and concentrated. The residue was purified via silica gel chromatography (100% EtOAc) to give the title compound (9 mg).

Workup

  1. additionwas added
  2. customyielded an 80% conversion of product via LCMS
  3. customThe reaction was quenched with NH4Cl
  4. extractionextracted with EtOAc (3×)
  5. washThe combined organic layers were washed with 0.5 N HCl, water, brine
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated
  8. customThe residue was purified via silica gel chromatography (100% EtOAc)

Sources & evidence

ORD record
ord-d17a3333a1624c0f8f63edd7d0cdbf32
Source dataset
uspto-grants-2011_02
Patent number
US07879875B2

Reaction notes

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