Piperidine → 1-((S)-1-((S)-2-(5-(4-bromophenyl)-1H-imidazol-2-yl)pyrrolidin-1-yl)-3-methyl-1-oxobutan-2-yl)thiourea

HRID 1873916Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1873916
[NH2:1][C@@H:2]([CH:22]([CH3:24])[CH3:23])[C:3]([N:5]1[CH2:9][CH2:8][CH2:7][C@H:6]1[C:10]1[NH:11][C:12]([C:15]2[CH:20]=[CH:19][C:18]([Br:21])=[CH:17][CH:16]=2)=[CH:13][N:14]=1)=[O:4].C([N:42]=[C:43]=[S:44])(=O)OCC1C2C=CC=CC=2C2C1=CC=CC=2.N1CCCCC1>C(Cl)Cl>[Br:21][C:18]1[CH:17]=[CH:16][C:15]([C:12]2[NH:11][C:10]([C@@H:6]3[CH2:7][CH2:8][CH2:9][N:5]3[C:3](=[O:4])[C@@H:2]([NH:1][C:43]([NH2:42])=[S:44])[CH:22]([CH3:24])[CH3:23])=[N:14][CH:13]=2)=[CH:20][CH:19]=1

Komponenten

5

Edukt 3

HCID 8082Piperidine2×HCID 4154759Fmoc isothiocyanateHCID 57610942(S)-2-amino-1-((S)-2-(5-(4-bromophenyl)-1H-imidazol-2-yl)pyrrolidin-1-yl)-3-methylbutan-1-one

Produkt 1

HCID 576109411-((S)-1-((S)-2-(5-(4-bromophenyl)-1H-imidazol-2-yl)pyrrolidin-1-yl)-3-methyl-1-oxobutan-2-yl)thiourea

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

To a solution of (S)-2-amino-1-((S)-2-(5-(4-bromophenyl)-1H-imidazol-2-yl)pyrrolidin-1-yl)-3-methylbutan-1-one (1.530 g, 3.91 mmol) in CH2Cl2 (10 mL) was added O-(9H-fluoren-9-yl)methyl carbonisothiocyanatidate (1.100 g, 3.91 mmol) as a solid in one portion. The mixture was allowed to stir at room temperature for 12 h. Piperidine (2 mL) was added to the mixture and it was allowed to stir at room temperature for 1 h. A further portion of piperidine (2 mL) was added and the solution allowed to stir 1 h. The solution was concentrated to dryness and the residue was purified by column chromatography (biotage, eluting with 5:4.5:0.5 hex:EtOAc:MeOH, and then 5% MeOH in EtOAc). The title compound as obtained as a light yellow glass (1.30 g, 74%). 1HNMR (300 MHz, DMSO-d6) δ 11.81 (s, H), 7.65 (d, J=8.8 Hz), 7.63-7.71 (m, overlap with previous peak, 2H total), 7.42-7.56 (m, 2H), 7.10-7.14 (m, 1H), 5.06 (dd, J=7.0, 3.0 Hz, 1H), 4.94 (app t, J=8.0 Hz, 1H), 4.72-4.76 and 4.56-4.62 (m, 1H, rotamers, 1:1 ratio), 3.77-3.90 (m, 1H), 2.07-2.14 (m, 2H), 1.90-1.98 (m, 3H), 0.93 (d, J=7.0 Hz, 3H), 0.84 (d, J=7.0 Hz, 3H). LCMS: Anal. Calcd. for C19H24BrN5OS: 449, 451. found: 450, 452 (M+H)+.

Aufarbeitung

  1. stirringto stir at room temperature for 1 h
  2. stirringto stir 1 h
  3. concentrationThe solution was concentrated to dryness
  4. customthe residue was purified by column chromatography (biotage
  5. washeluting with 5:4.5:0.5 hex

Quellen und Nachweise

ORD-Eintrag
ord-6d364cec8ffd488eadf94befbbe84dac
Quelldatensatz
uspto-grants-2012_11
Patentnummer
US08303944B2

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