Ethyl piperidine-2-carboxylate → 1-[(2S)-2-((3S)-3-{[(6-Chloro-2-naphthyl)sulfonyl]amino}-2-oxopyrrolidin-1-yl)propanoyl]piperidine-2-carboxylic acid

HRID 1765660Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1765660
[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]([CH3:25])[C:22](O)=[O:23])[C:17]1=[O:26])(=[O:14])=[O:13])[CH:6]=[CH:5]2.Cl.CN(C)CCCN=C=NCC.C1C=CC2N(O)N=NC=2C=1.[NH:49]1[CH2:59][CH2:58][CH2:57][CH2:56][CH:50]1[C:51]([O:53]CC)=[O:52]>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]([CH3:25])[C:22]([N:49]3[CH2:59][CH2:58][CH2:57][CH2:56][CH:50]3[C:51]([OH:53])=[O:52])=[O:23])[C:17]1=[O:26])(=[O:13])=[O:14])[CH:6]=[CH:5]2

Komponenten

7

Edukt 4

HCID 27517Ethyl piperidine-2-carboxylateHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 69058818(2S)-2-((3S)-3-{[(6-chloro-2-naphthyl)sulfonyl]amino}-2-oxopyrrolidin-1-yl)propanoic acid

Produkt 1

HCID 693291741-[(2S)-2-((3S)-3-{[(6-Chloro-2-naphthyl)sulfonyl]amino}-2-oxopyrrolidin-1-yl)propanoyl]piperidine-2-carboxylic acidAusbeute 21,9 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6344DichloromethaneLösungsmittelHCID 8471TriethylamineLösungsmittel

Versuchsvorschrift

To a solution of (2S)-2-((3S)-3-{[(6-chloro-2-naphthyl)sulfonyl]amino}-2-oxopyrrolidin-1-yl)propanoic acid (0.025 g) in DCM (10 ml) were added 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (0.036 g), HOBT (0.026 g) and triethylamine (0.026 ml) and the mixture was stirred at room temperature for 30 min. Ethyl pipecolinate (0.030 g) was added and the resultant mixture stirred at room temperature for 16 h. The mixture was partitioned between DCM and water. The aqueous layer was re-extracted with DCM and the combined, dried (over magnesium sulphate) organic extracts were concentrated under reduced pressure. The residue was then dissolved in a mixture of THF (1 ml) and water (1 ml), treated with lithium hydroxide (0.005 g) and stirred at room temperature for 18 h. The reaction mixture was acidified to pH5 using hydrochloric acid (2N) and concentrated under reduced pressure. The residue was purified using SPE (aminopropyl stationary phase, washed with methanol and eluted with 10% hydrochloric acid in methanol) to give the title compound (0.007 g) as white solid.

Aufarbeitung

  1. customThe mixture was partitioned between DCM and water
  2. extractionThe aqueous layer was re-extracted with DCM
  3. dry with materialdried (over magnesium sulphate) organic extracts
  4. concentrationwere concentrated under reduced pressure
  5. dissolutionThe residue was then dissolved in a mixture of THF (1 ml) and water (1 ml)
  6. additiontreated with lithium hydroxide (0.005 g)
  7. stirringstirred at room temperature for 18 h
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified
  10. washSPE (aminopropyl stationary phase, washed with methanol and eluted with 10% hydrochloric acid in methanol)

Quellen und Nachweise

ORD-Eintrag
ord-58d08d9bb02c4b0cae2063b0b94d0042
Quelldatensatz
uspto-grants-2007_06
Patentnummer
US07226929B2

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