1,2-Dichloroethane → HCID 21837225, compound

HRID 1740612Notes

Reaction equation

HRID 1740612 reaction equation
[F:1][C:2]([F:17])([F:16])[CH2:3][O:4][C:5]1[CH:10]=[C:9]([F:11])[CH:8]=[CH:7][C:6]=1[CH2:12][C:13]([OH:15])=O.[C:18]([CH:21]1[CH2:26][N:25]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=2[CH3:33])[CH2:24][CH2:23][NH:22]1)(=[O:20])[NH2:19].C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl.CCN(C(C)C)C(C)C>CN(C=O)C>[F:11][C:9]1[CH:8]=[CH:7][C:6]([CH2:12][C:13]([N:22]2[CH2:23][CH2:24][N:25]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=3[CH3:33])[CH2:26][CH:21]2[C:18](=[O:20])[NH2:19])=[O:15])=[C:5]([O:4][CH2:3][C:2]([F:1])([F:17])[F:16])[CH:10]=1

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 154305682-Carbamoyl-4-(2-methylphenyl)piperazineHCID 54304074HCID 54304074, compound

Product 1

HCID 21837225HCID 21837225, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of 2-(2,2,2-trifluoroethoxy)-4-fluorophenylacetic acid (0.15 g, 0.60 mmol) from Step 5 above and 2-carbamoyl-4-(2-methylphenyl)piperazine (0.13 g, 0.66 mmol) from Step 4 of Example 1 in DMF (3 mL) was added HOBT (0.11 g, 0.78 mmol), EDC (0.17 g, 0.9 mmol), and DIEA (0.16 mL, 0.9 mmol). The solution was stirred at ambient temperature for 14 h and the solvent was removed under reduced pressure. The residue was partitioned between EtOAc (50 mL) and 0.25 M aqueous citric acid (25 mL). The organic phase was separated and washed with H2O (10 mL) and saturated aqueous NaHCO3 (25 mL). The organic phase was dried (MgSO4), filtered, and the solvent was removed under reduced pressure. The residue was purified by pressurized silica gel column chromatography using 5:95 MeOH:CH2Cl2 as eluant. Evaporation of the product-containing fractions gave the title compound as an amorphous solid. HPLC retention time=9.16 min (method A) TLC Rf =0.25 (5:95 MeOH:CH2Cl2); FAB MS: m/z=454 (M+ +H), 0.4 CH2Cl2 ; combustion analysis: C22H23F4N3O3, 0.4 CH2Cl2 ; Calculated C, 57.43; H, 5.12; N, 8.97; Found C, 57.44; H, 4.89; N, 9.22

Workup

  1. customthe solvent was removed under reduced pressure
  2. customThe residue was partitioned between EtOAc (50 mL) and 0.25 M aqueous citric acid (25 mL)
  3. customThe organic phase was separated
  4. washwashed with H2O (10 mL) and saturated aqueous NaHCO3 (25 mL)
  5. dry with materialThe organic phase was dried (MgSO4)
  6. filtrationfiltered
  7. customthe solvent was removed under reduced pressure
  8. customThe residue was purified by pressurized silica gel column chromatography
  9. customEvaporation of the product-containing fractions

Sources & evidence

ORD record
ord-eed113ae31bb4f18a14efa2f93d68722
Source dataset
uspto-grants-1999_10
Patent number
US05968938

Reaction notes

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