1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride → (R)-3-(3-fluoro-4-trifluoromethoxy-benzylcarbamoyl)-4-(4-trifluoromethoxy-benzenesulfonyl)-piperazine-1-carboxylic acid tert-butyl ester

HRID 908628Notes

Reaction equation

HRID 908628 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([S:14]([C:17]2[CH:22]=[CH:21][C:20]([O:23][C:24]([F:27])([F:26])[F:25])=[CH:19][CH:18]=2)(=[O:16])=[O:15])[C@@H:10]([C:28](O)=[O:29])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.C(N=C=NCCCN(C)C)C.O.ON1C2C=CC=CC=2N=N1.[F:54][C:55]1[CH:56]=[C:57]([CH:60]=[CH:61][C:62]=1[O:63][C:64]([F:67])([F:66])[F:65])[CH2:58][NH2:59]>C(Cl)(Cl)Cl>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([S:14]([C:17]2[CH:22]=[CH:21][C:20]([O:23][C:24]([F:27])([F:26])[F:25])=[CH:19][CH:18]=2)(=[O:16])=[O:15])[C@@H:10]([C:28](=[O:29])[NH:59][CH2:58][C:57]2[CH:60]=[CH:61][C:62]([O:63][C:64]([F:65])([F:66])[F:67])=[C:55]([F:54])[CH:56]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 177506743-Fluoro-4-(trifluoromethoxy)benzylamineHCID 59703724(R)-4-(4-trifluoromethoxy-benzenesulfonyl)-piperazine-1,3-dicarboxylic acid 1-tert-butyl ester

Product 1

HCID 59703721(R)-3-(3-fluoro-4-trifluoromethoxy-benzylcarbamoyl)-4-(4-trifluoromethoxy-benzenesulfonyl)-piperazine-1-carboxylic acid tert-butyl esterYield 78.4%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

To a solution of the compound (1.35 g) obtained in Example 783, Step 2 in chloroform (15 ml) were added 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (625 mg), 1-hydroxybenzotriazole hydrate (499 mg) and 3-fluoro-4-trifluoromethoxybenzylamine (620 mg) with stirring under ice-cooling. After stirring overnight at room temperature, the reaction mixture was partitioned by adding saturated aqueous sodium hydrogen carbonate solution and chloroform, and the aqueous layer was re-extracted twice with chloroform. The organic layers were combined, dried over anhydrous magnesium sulfate, filtrated, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=1:l) to give the title compound (1.50 g).

Workup

  1. temperaturecooling
  2. stirringAfter stirring overnight at room temperature
  3. customthe reaction mixture was partitioned
  4. additionby adding saturated aqueous sodium hydrogen carbonate solution and chloroform
  5. extractionthe aqueous layer was re-extracted twice with chloroform
  6. dry with materialdried over anhydrous magnesium sulfate
  7. filtrationfiltrated
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by silica gel column chromatography (hexane:ethyl acetate=1:l)

Sources & evidence

ORD record
ord-1a4b63ce9e0742a2a498548845237910
Source dataset
uspto-grants-2011_09
Patent number
US08017612B2

Reaction notes

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