1,2-Dichloroethane → N-[2-(Carbamoylamino)-1-(2,3-dichlorophenyl)ethyl]-2-[3-(4-chlorophenyl)-5-oxo-4-(3,3,3-trifluoropropyl)-4,5-dihydro-1H-1,2,4-triazol-1-yl]acetamide

HRID 220707Notes

Reaction equation

HRID 220707 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]([CH2:13][CH2:14][C:15]([F:18])([F:17])[F:16])[C:11](=[O:19])[N:10]([CH2:20][C:21](O)=[O:22])[N:9]=2)=[CH:4][CH:3]=1.[CH2:24]([Cl:27])[CH2:25][Cl:26].[CH:28]1[CH:29]=[CH:30][C:31]2[N:36](O)N=[N:34][C:32]=2[CH:33]=1.C(N(CC)C(C)C)(C)C.C[N:48]([CH:50]=[O:51])C>C(OCC)(=O)C>[C:50]([NH:34][CH2:32][CH:31]([NH:36][C:21](=[O:22])[CH2:20][N:10]1[C:11](=[O:19])[N:12]([CH2:13][CH2:14][C:15]([F:18])([F:16])[F:17])[C:8]([C:5]2[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=2)=[N:9]1)[C:30]1[CH:29]=[CH:28][CH:33]=[C:25]([Cl:26])[C:24]=1[Cl:27])(=[O:51])[NH2:48]

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 6228DimethylformamideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 59536724[3-(4-Chlorophenyl)-5-oxo-4-(3,3,3-trifluoropropyl)-4,5-dihydro-1H-1,2,4-triazol-1-yl]acetic acid

Product 1

HCID 46917113N-[2-(Carbamoylamino)-1-(2,3-dichlorophenyl)ethyl]-2-[3-(4-chlorophenyl)-5-oxo-4-(3,3,3-trifluoropropyl)-4,5-dihydro-1H-1,2,4-triazol-1-yl]acetamide

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

Of the compound from Example 177A, 162 mg (0.46 mmol), 145 mg (0.51 mmol) of the compound from Example 153A, 107 mg (0.56 mmol) of EDC, 75 mg (0.56 mmol) of HOBt and 97 μl (0.56 mmol) of N,N-diisopropylethylamine were stirred in 5.4 ml of DMF at RT overnight. The solution was diluted with 150 ml of ethyl acetate and extracted in succession twice each with 1M hydrochloric acid and with 1M aqueous sodium hydrogen carbonate solution. The organic phase was dried over sodium sulphate and freed from the volatile components on a rotary evaporator. The residue was purified by preparative HPLC [Method 20]. The product fraction was freed from the solvents on a rotary evaporator and the residue was dried in an HV. This gave 163 mg (61% of theory) of the title compound.

Workup

  1. extractionextracted in succession twice each with 1M hydrochloric acid
  2. dry with materialThe organic phase was dried over sodium sulphate
  3. customfreed from the volatile components on a rotary evaporator
  4. customThe residue was purified by preparative HPLC [Method 20]
  5. customThe product fraction was freed from the solvents on a rotary evaporator
  6. customthe residue was dried in an HV

Sources & evidence

ORD record
ord-ea35577f2ce94e369fe21a794ab437b4
Source dataset
uspto-grants-2012_06
Patent number
US08202895B2

Reaction notes

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