Diisopropylethylamine → rac-[(3R,4S)-4-(3,4-Dichloro-phenyl)-1-(1-[1,3,4]thiadiazol-2-yl-piperidine-4-carbonyl)-pyrrolidin-3-yl]-methyl-carbamic acid 4-fluoro-phenyl ester

HRID 587338Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 587338
[F:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][C:9](=[O:33])[N:10]([C@@H:12]2[C@@H:16]([C:17]3[CH:22]=[CH:21][C:20]([Cl:23])=[C:19]([Cl:24])[CH:18]=3)[CH2:15][N:14]([C:25]([CH:27]3[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]3)=[O:26])[CH2:13]2)[CH3:11])=[CH:4][CH:3]=1.Br[C:35]1[S:36][CH:37]=[N:38][N:39]=1.C(N(CC)C(C)C)(C)C>CN1CCCC1=O.C(OCC)(=O)C>[F:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][C:9](=[O:33])[N:10]([C@@H:12]2[C@@H:16]([C:17]3[CH:22]=[CH:21][C:20]([Cl:23])=[C:19]([Cl:24])[CH:18]=3)[CH2:15][N:14]([C:25]([CH:27]3[CH2:32][CH2:31][N:30]([C:35]4[S:36][CH:37]=[N:38][N:39]=4)[CH2:29][CH2:28]3)=[O:26])[CH2:13]2)[CH3:11])=[CH:4][CH:3]=1

Komponenten

6

Edukt 3

HCID 81531DiisopropylethylamineHCID 27951982-Bromo-1,3,4-thiadiazoleHCID 58303080[(3R,4S)-4-(3,4-Dichloro-phenyl)-1-(piperidine-4-carbonyl)-pyrrolidin-3-yl]-methyl-carbamic acid 4-fluoro-phenyl ester

Produkt 1

HCID 58303145rac-[(3R,4S)-4-(3,4-Dichloro-phenyl)-1-(1-[1,3,4]thiadiazol-2-yl-piperidine-4-carbonyl)-pyrrolidin-3-yl]-methyl-carbamic acid 4-fluoro-phenyl esterAusbeute 32 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 8857Ethyl AcetateLösungsmittelHCID 13387N-methyl-2-pyrrolidoneLösungsmittel

Versuchsvorschrift

To a solution of rac-[(3R,4S)-4-(3,4-dichloro-phenyl)-1-(piperidine-4-carbonyl)-pyrrolidin-3-yl]-methyl-carbamic acid 4-fluoro-phenyl ester (100 mg, 0.20 mmol) in N-methylpyrrolidinone (1 mL) was added 2-bromo-1,3,4-thiadiazole (50 mg, 0.30 mmol) and N,N-diisopropyl ethyl amine (69 μl, 0.40 mmol). The solution was irradiated in the microwave for 35 min at 150° C. The reaction mixture was diluted with ethyl acetate (15 mL) and washed with an aqueous solution of sodium carbonate (1 M, 15 mL). The organic layer was separated and washed with brine (15 mL) and the aqueous layers were extracted with ethyl acetate (20 mL). The combined organic layers were dried over sodium sulfate and concentrated. Purification by chromatography (SiO2, ethyl acetate:methanol=100:0 to 80:20) afforded the title compound (37 mg, 32%) as an off-white foam. MS m/e: 578.1 [M]+.

Aufarbeitung

  1. customThe solution was irradiated in the microwave for 35 min at 150° C
  2. washwashed with an aqueous solution of sodium carbonate (1 M, 15 mL)
  3. customThe organic layer was separated
  4. washwashed with brine (15 mL)
  5. extractionthe aqueous layers were extracted with ethyl acetate (20 mL)
  6. dry with materialThe combined organic layers were dried over sodium sulfate
  7. concentrationconcentrated
  8. customPurification by chromatography (SiO2, ethyl acetate:methanol=100:0 to 80:20)

Quellen und Nachweise

ORD-Eintrag
ord-aba469d1b2d04503bbfcea129ac21d75
Quelldatensatz
uspto-grants-2016_01
Patentnummer
US09226916B2

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