Trifluoroacetic acid → N-{1-[(2R)-2-((3S)-3-{[(6-Chloro-2-naphthyl)sulfonyl]amino}-2-oxopyrrolidin-1-yl)propanoyl]piperidin-3-yl}benzamide

HRID 1765655

Reaction equation

HRID 1765655 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH:8]=[C:7]([S:12]([NH:15][C@H:16]1[CH2:20][CH2:19][N:18]([C@H:21]([CH3:29])[C:22](OC(C)(C)C)=[O:23])[C:17]1=[O:30])(=[O:14])=[O:13])[CH:6]=[CH:5]2.FC(F)(F)C(O)=O.Cl.CN(C)CCCN=C=NCC.C1C=CC2N(O)N=NC=2C=1.[NH:60]1[CH2:65][CH2:64][CH2:63][CH:62]([NH:66][C:67](=[O:74])[C:68]2[CH:73]=[CH:72][CH:71]=[CH:70][CH:69]=2)[CH2:61]1>C(Cl)Cl.C(N(CC)CC)C>[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH:8]=[C:7]([S:12]([NH:15][C@H:16]1[CH2:20][CH2:19][N:18]([C@H:21]([CH3:29])[C:22]([N:60]3[CH2:65][CH2:64][CH2:63][CH:62]([NH:66][C:67](=[O:74])[C:68]4[CH:69]=[CH:70][CH:71]=[CH:72][CH:73]=4)[CH2:61]3)=[O:23])[C:17]1=[O:30])(=[O:14])=[O:13])[CH:6]=[CH:5]2

Participants

8

Reactant 5

HCID 6422Trifluoroacetic acidHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 22017045N-(piperidin-3-yl)benzamideHCID 69222063tert-butyl (2R)-2-((3S)-3-{[(6-chloro-2-naphthyl)sulfonyl]amino)-2-oxopyrrolidin-1-yl)propanoate

Product 1

HCID 69329876N-{1-[(2R)-2-((3S)-3-{[(6-Chloro-2-naphthyl)sulfonyl]amino}-2-oxopyrrolidin-1-yl)propanoyl]piperidin-3-yl}benzamideYield 37.3%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8471TriethylamineSolvent

Procedure

A solution of tert-butyl (2R)-2-((3S)-3-{[(6-chloro-2-naphthyl)sulfonyl]amino}-2-oxopyrrolidin-1-yl)propanoate (0.025 g) in DCM (1 ml) was treated with trifluoroacetic acid (1 ml) and stirred at room temperature for 2 h. The mixture was then concentrated under reduced pressure to give an oil which was subsequently treated with 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (0.013 g), HOBT (0.009 g) and triethylamine (0.023 ml). After stirring at room temperature for 1 h, N-piperidin-3-ylbenzamide (0.015 g) was added and stirring was continued for 48 h. The reaction mixture was partitioned between DCM and water. The organic extract was concentrated under reduced pressure and the residue purified using SPE (silica, eluting with cyclohexane:ethyl acetate 5:1, 3:1, 1:1, 1:3 and ethyl acetate) to give the title compound (0.012 g) as a colourless gum.

Workup

  1. concentrationThe mixture was then concentrated under reduced pressure
  2. customto give an oil which
  3. stirringAfter stirring at room temperature for 1 h
  4. stirringstirring
  5. waitwas continued for 48 h
  6. customThe reaction mixture was partitioned between DCM and water
  7. extractionThe organic extract
  8. concentrationwas concentrated under reduced pressure
  9. customthe residue purified
  10. washSPE (silica, eluting with cyclohexane:ethyl acetate 5:1, 3:1, 1:1, 1:3 and ethyl acetate)

Sources & evidence

ORD record
ord-4529725f12b8405fb916b3afeb2e3d66
Source dataset
uspto-grants-2007_06
Patent number
US07226929B2

Linked notes

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