1-Hydroxybenzotriazole → N-(5-bromo-2-fluorophenylmethyl)-2-[3-(4-chlorophenyl)-4-cyclopropyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl]acetamide

HRID 660924Notes

Reaction equation

HRID 660924 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]([CH:13]3[CH2:15][CH2:14]3)[C:11](=[O:16])[N:10]([CH2:17][C:18](O)=[O:19])[N:9]=2)=[CH:4][CH:3]=1.Cl.[Br:22][C:23]1[CH:24]=[CH:25][C:26]([F:31])=[C:27]([CH:30]=1)[CH2:28][NH2:29].C1C=CC2N(O)N=NC=2C=1.C(N(CC)C(C)C)(C)C.CCN=C=NCCCN(C)C.Cl>CN(C)C=O.O>[Br:22][C:23]1[CH:24]=[CH:25][C:26]([F:31])=[C:27]([CH2:28][NH:29][C:18](=[O:19])[CH2:17][N:10]2[C:11](=[O:16])[N:12]([CH:13]3[CH2:15][CH2:14]3)[C:8]([C:5]3[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=3)=[N:9]2)[CH:30]=1

Participants

8

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27249035-Bromo-2-fluorobenzylamine hydrochlorideHCID 42632357[3-(4-chlorophenyl)-4-cyclopropyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl]acetic acid

Product 1

HCID 58012165N-(5-bromo-2-fluorophenylmethyl)-2-[3-(4-chlorophenyl)-4-cyclopropyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl]acetamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

40.0 mg (0.144 mmol) of [3-(4-chlorophenyl)-4-cyclopropyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl]-acetic acid from Example 93A, 36.0 mg (0.150 mmol) of 5-bromo-2-fluorobenzylamine hydrochloride, 22.1 mg (0.163 mmol) of HOBt and 17.6 mg (0.136 mmol) of N,N-diisopropyl-ethylamine are placed in 1.5 ml of dimethylformamide and treated with 33.9 mg (0.177 mmol) of EDC hydrochloride. This is stirred overnight at room temperature, then diluted with 15 ml of water and extracted with ethyl acetate. After evaporation of the organic phase, the crude product is purified by preparative HPLC [Method 13]. 21 mg (32% of theory) of the target compound are thus obtained.

Workup

  1. extractionextracted with ethyl acetate
  2. customAfter evaporation of the organic phase
  3. customthe crude product is purified by preparative HPLC [Method 13]
  4. custom21 mg (32% of theory) of the target compound are thus obtained

Sources & evidence

ORD record
ord-bb009a075d7e4ebb94db55b5121c3550
Source dataset
uspto-grants-2011_12
Patent number
US08084481B2

Reaction notes

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