1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride → 2-[(R)-3-[(6-isopropyl-pyridin-3-ylmethyl)-carbamoyl]-4-(4-trifluoromethoxy-benzenesulfonyl)-piperazin-1-yl]-4-methyl-thiazole-5-carboxylic acid tert-butyl ester

HRID 908595Notes

Reaction equation

HRID 908595 reaction equation
[C:1]([O:5][C:6]([C:8]1[S:12][C:11]([N:13]2[CH2:18][CH2:17][N:16]([S:19]([C:22]3[CH:27]=[CH:26][C:25]([O:28][C:29]([F:32])([F:31])[F:30])=[CH:24][CH:23]=3)(=[O:21])=[O:20])[C@@H:15]([C:33]([OH:35])=O)[CH2:14]2)=[N:10][C:9]=1[CH3:36])=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH:37]([C:40]1[N:45]=[CH:44][C:43]([CH2:46][NH2:47])=[CH:42][CH:41]=1)([CH3:39])[CH3:38].O.ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C>CN(C)C=O>[C:1]([O:5][C:6]([C:8]1[S:12][C:11]([N:13]2[CH2:18][CH2:17][N:16]([S:19]([C:22]3[CH:27]=[CH:26][C:25]([O:28][C:29]([F:32])([F:30])[F:31])=[CH:24][CH:23]=3)(=[O:21])=[O:20])[C@@H:15]([C:33](=[O:35])[NH:47][CH2:46][C:43]3[CH:44]=[N:45][C:40]([CH:37]([CH3:39])[CH3:38])=[CH:41][CH:42]=3)[CH2:14]2)=[N:10][C:9]=1[CH3:36])=[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 17854197[6-(Propan-2-yl)pyridin-3-yl]methanamineHCID 59703741(R)-4-(5-tert-butoxycarbonyl-4-methyl-thiazol-2-yl)-1-(4-trifluoromethoxy-benzenesulfonyl)-piperazine-2-carboxylic acid

Product 1

HCID 597038392-[(R)-3-[(6-isopropyl-pyridin-3-ylmethyl)-carbamoyl]-4-(4-trifluoromethoxy-benzenesulfonyl)-piperazin-1-yl]-4-methyl-thiazole-5-carboxylic acid tert-butyl esterYield 86.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a mixed solution of the compound (55 mg) obtained in Step 6, [(6-isopropylpyridin-3-yl)methyl]amine (24 mg) and 1-hydroxybenzotriazole hydrate (23 mg) in N,N-dimethylformamide (660 μl) was added, with stirring at room temperature, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (29 mg). After stirring at room temperature for 3 hr, the reaction mixture was partitioned by adding saturated aqueous sodium hydrogen carbonate solution and ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, filtrated, and concentrated under reduced pressure. The residue was purified by thin layer chromatography (ethyl acetate:n-hexane=3:2) to give the title compound (59 mg).

Workup

  1. stirringAfter stirring at room temperature for 3 hr
  2. customthe reaction mixture was partitioned
  3. additionby adding saturated aqueous sodium hydrogen carbonate solution and ethyl acetate
  4. washThe organic layer was washed with saturated brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltrated
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by thin layer chromatography (ethyl acetate:n-hexane=3:2)

Sources & evidence

ORD record
ord-09ebb1cbbe7e43e8b8f6b87a67e0c103
Source dataset
uspto-grants-2011_09
Patent number
US08017612B2

Reaction notes

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