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

HRID 908620Notes

Reaction equation

HRID 908620 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].O.ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.[F:54][CH:55]([F:66])[O:56][C:57]1[CH:64]=[CH:63][C:60]([CH2:61][NH2:62])=[CH:59][C:58]=1[F:65]>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:18]=[CH:19][C:20]([O:23][C:24]([F:25])([F:27])[F:26])=[CH:21][CH:22]=2)(=[O:16])=[O:15])[C@@H:10]([C:28](=[O:29])[NH:62][CH2:61][C:60]2[CH:63]=[CH:64][C:57]([O:56][CH:55]([F:54])[F:66])=[C:58]([F:65])[CH:59]=2)[CH2:9]1)=[O:7])([CH3:3])([CH3:2])[CH3:4]

Participants

6

Reactant 4

HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 59703724(R)-4-(4-trifluoromethoxy-benzenesulfonyl)-piperazine-1,3-dicarboxylic acid 1-tert-butyl esterHCID 59703736[4-(Difluoromethoxy)-3-fluorophenyl]methanamine

Product 1

HCID 59703864(R)-3-(4-difluoromethoxy-3-fluoro-benzylcarbamoyl)-4-(4-trifluoromethoxy-benzenesulfonyl)-piperazine-1-carboxylic acid tert-butyl esterYield 109.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a solution of the compound (1.83 g) obtained in Example 783, Step 2 in N,N-dimethylformamide (10 ml) were successively added, with stirring under ice-cooling, 1-hydroxybenzotriazole hydrate (677 mg), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (847 mg) and a solution of 4-difluoromethoxy-3-fluorobenzylamine (806 mg) in N,N-dimethylformamide (3 ml). After stirring overnight at room temperature, the mixture was partitioned by adding ethyl acetate and saturated aqueous sodium hydrogen carbonate solution. The aqueous layer was extracted with ethyl acetate, the combined organic layer was washed successively with saturated aqueous sodium hydrogen carbonate solution and water. The organic layer was dried over anhydrous magnesium sulfate, filtrated, and concentrated under reduced pressure to give the title compound (2.76 g).

Workup

  1. temperaturecooling
  2. stirringAfter stirring overnight at room temperature
  3. customthe mixture was partitioned
  4. additionby adding ethyl acetate and saturated aqueous sodium hydrogen carbonate solution
  5. extractionThe aqueous layer was extracted with ethyl acetate
  6. washthe combined organic layer was washed successively with saturated aqueous sodium hydrogen carbonate solution and water
  7. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  8. filtrationfiltrated
  9. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-ce4f912678ce4f908e05b1d1139bb18b
Source dataset
uspto-grants-2011_09
Patent number
US08017612B2

Reaction notes

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