4-Methylmorpholine → ethyl (3S,4R)-4-{[(4-chloro-3-cyano-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-propoxypiperidine-1-carboxylate

HRID 655786Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 655786
[Cl:1][C:2]1[C:3]([C:11]#[N:12])=[C:4]([C:8]([OH:10])=O)[NH:5][C:6]=1[CH3:7].ClC1C=C(C([NH:22][C@H:23]2[CH2:28][CH2:27][N:26]([C:29]([O:31][CH2:32][CH3:33])=[O:30])[CH2:25][C@H:24]2[O:34][CH2:35][CH2:36][CH3:37])=O)NC=1C.ON1C2C=CC=CC=2N=N1.CN1CCOCC1>ClCCl>[Cl:1][C:2]1[C:3]([C:11]#[N:12])=[C:4]([C:8]([NH:22][C@@H:23]2[CH2:28][CH2:27][N:26]([C:29]([O:31][CH2:32][CH3:33])=[O:30])[CH2:25][C@@H:24]2[O:34][CH2:35][CH2:36][CH3:37])=[O:10])[NH:5][C:6]=1[CH3:7]

Komponenten

6

Edukt 4

HCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 594025744-chloro-3-cyano-5-methyl-1H-pyrrole-2-carboxylic acid2×HCID 66707582ethyl (3R,4S)-4-{[(4-chloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-propoxypiperidine-1-carboxylate2×

Produkt 1

HCID 59402480ethyl (3S,4R)-4-{[(4-chloro-3-cyano-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-propoxypiperidine-1-carboxylateAusbeute 76 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

To a solution of 4-chloro-3-cyano-5-methyl-1H-pyrrole-2-carboxylic acid (Intermediate 16, 2 g, 8.69 mmol) and ethyl (3S,4R)-4-amino-3-propoxypiperidine-1-carboxylate (see Intermediate 73, 1.59 g, 8.695 mmol) in dichloromethane (150 mL) was added N-Hydroxybenzotriazole (1.6 g, 10.43 mM) and N-methylmorpholine (2.63 g, 26.08 mmol). The reaction mixture was stirred for 1 h at room temperature and 1-Ethyl-3-(3-dimethyl amino propyl)carbodiimide hydrochloride (2.87 g, 15.6 mM) was added. The resulting reaction mixture was stirred at room temperature overnight. The reaction mixture was quenched with 2N hydrochloric acid (50 mL) and the layers were separated. The organic layer was washed with sodium bicarbonate (40 mL), water (60 mL) and finally with brine successively and dried over anhydrous sodium sulphate, filtered, concentrated under vacuum to afford ethyl (3S,4R)-4-{[(4-chloro-3-cyano-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-propoxypiperidine-1-carboxylate 2.6 g (76%) as solid.

Aufarbeitung

  1. customThe resulting reaction mixture
  2. stirringwas stirred at room temperature overnight
  3. customThe reaction mixture was quenched with 2N hydrochloric acid (50 mL)
  4. customthe layers were separated
  5. washThe organic layer was washed with sodium bicarbonate (40 mL), water (60 mL) and finally with brine successively
  6. dry with materialdried over anhydrous sodium sulphate
  7. filtrationfiltered
  8. concentrationconcentrated under vacuum

Quellen und Nachweise

ORD-Eintrag
ord-e3b2685465044a7b8012eeaf7c06a864
Quelldatensatz
uspto-grants-2011_12
Patentnummer
US08071605B2

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