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

HRID 908624Notes

Reaction equation

HRID 908624 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]([C:23]([F:26])([F:25])[F:24])=[CH:19][CH:18]=2)(=[O:16])=[O:15])[C@@H:10]([C:27](O)=[O:28])[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:53][C:54]1[CH:55]=[C:56]([CH:59]=[CH:60][C:61]=1[O:62][C:63]([F:66])([F:65])[F:64])[CH2:57][NH2:58]>CN(C)C=O>[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]([C:23]([F:24])([F:25])[F:26])=[CH:19][CH:18]=2)(=[O:16])=[O:15])[C@@H:10]([C:27](=[O:28])[NH:58][CH2:57][C:56]2[CH:59]=[CH:60][C:61]([O:62][C:63]([F:64])([F:65])[F:66])=[C:54]([F:53])[CH:55]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 177506743-Fluoro-4-(trifluoromethoxy)benzylamineHCID 59703735(R)-4-(4-trifluoromethyl-benzenesulfonyl)-piperazine-1,3-dicarboxylic acid 1-tert-butyl ester

Product 1

HCID 59703799(R)-3-(3-fluoro-4-trifluoromethoxy-benzylcarbamoyl)-4-(4-trifluoromethyl-benzenesulfonyl)-piperazine-1-carboxylic acid tert-butyl esterYield 95.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of the compound (1.24 g) obtained in Example 1001, Step 1 in N,N-dimethylformamide (12 ml) were added, with stirring under ice-cooling, 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (0.65 g), 1-hydroxybenzotriazole hydrate (0.52 g) and the compound (0.59 g) obtained in Step 3. After stirring overnight at room temperature, the reaction mixture was partitioned by adding saturated aqueous sodium hydrogen carbonate solution and ethyl acetate. The organic layer was washed successively with water and saturated brine, dried over anhydrous sodium sulfate, filtrated, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (methanol:chloroform=4:96-6:94) to give the title compound (1.70 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 ethyl acetate
  5. washThe organic layer was washed successively with water and saturated brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltrated
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by silica gel column chromatography (methanol:chloroform=4:96-6:94)

Sources & evidence

ORD record
ord-1f0dd849a13249f286ba5c88ef00250d
Source dataset
uspto-grants-2011_09
Patent number
US08017612B2

Reaction notes

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