2-Pyridinecarboxaldehyde → (s)-1-(9h-Fluoren-9-yl)-14,14-dimethyl-3,12-dioxo-10-(pyridin-2-ylmethyl)-2,13-dioxa-4,10-diazapentadecane-5-carboxylic acid

HRID 1043369Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1043369
[NH:1]([C:11]([O:13][CH2:14][CH:15]1[C:27]2[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=2)[C:21]2[C:16]1=[CH:17][CH:18]=[CH:19][CH:20]=2)=[O:12])[C@H:2]([C:8]([OH:10])=[O:9])[CH2:3][CH2:4][CH2:5][CH2:6][NH2:7].Cl.[N:29]1[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=1[CH:35]=O.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].[C:51]([O:55][C:56]([CH3:59])([CH3:58])[CH3:57])(=[O:54])[CH:52]=O>ClCCCl.O>[CH:17]1[C:16]2[CH:15]([CH2:14][O:13][C:11](=[O:12])[NH:1][C@H:2]([C:8]([OH:10])=[O:9])[CH2:3][CH2:4][CH2:5][CH2:6][N:7]([CH2:35][C:30]3[CH:31]=[CH:32][CH:33]=[CH:34][N:29]=3)[CH2:52][C:51](=[O:54])[O:55][C:56]([CH3:59])([CH3:58])[CH3:57])[C:27]3[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=3)[C:21]=2[CH:20]=[CH:19][CH:18]=1

Komponenten

7

Edukt 4

HCID 142732-PyridinecarboxaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 10986247Tert-butyl 2-oxoacetateHCID 11858928(2S)-6-amino-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)hexanoic acid hydrochloride

Produkt 1

HCID 59408713(s)-1-(9h-Fluoren-9-yl)-14,14-dimethyl-3,12-dioxo-10-(pyridin-2-ylmethyl)-2,13-dioxa-4,10-diazapentadecane-5-carboxylic acidAusbeute 28 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 111,2-DichloroethaneLösungsmittelHCID 962WaterLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

A suspension of Fmoc-Lys-OH.HCl (4.859 g, 12 mmol) and 2-pyridinecarboxaldehyde (1.285 g, 12 mmol) in DCE (100 mL) was refluxed for 30 min under nitrogen. The reaction mixture was cooled to 0° C., and treated sequentially with NaBH(OAc)3 (6.36 g, 30 mmol) and crude tert-butyl glyoxalate (2.34 g, 18 mmol) The reaction mixture was stirred at room temperature for overnight and decomposed with water. The reaction mixture was extracted with DCM. The organic layer was dried and concentrated under reduced pressure. The residue was purified by flash chromatography over silica gel to afford ((S)-1-(9H-fluoren-9-yl)-14,14-dimethyl-3,12-dioxo-10-(pyridin-2-ylmethyl)-2,13-dioxa-4,10-diazapentadecane-5-carboxylic acid (1.924 g, 28%). 1H NMR (400 MHz, CDCl3) 8.89 (d, J=4.4 Hz, 1H), 8.06 (d, J=8.0 Hz, 1H), 8.02 (d, J=7.6 Hz, 2H), 7.88 (t, J=5.8 Hz, 2H), 7.81 (d, J=7.6 Hz, 1H), 7.66 (t, J=7.4 Hz, 2H), 7.60-7.53 (m, 4H), 6.03 (d, J=7.2 Hz, 1H), 4.67-4.22 (m, 8H), 3.64-3.53 (m, 2H), 3.12 (t, J=6.8 Hz, 2H), 2.19-2.08 (m, 2H), 1.92-1.79 (m, 2H), 1.73 (s, 9H); MS (ESI), 564 (M+H)+.

Aufarbeitung

  1. temperaturewas refluxed for 30 min under nitrogen
  2. extractionThe reaction mixture was extracted with DCM
  3. customThe organic layer was dried
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by flash chromatography over silica gel

Quellen und Nachweise

ORD-Eintrag
ord-2a1739e315884df68fefcfe49b9c9b6c
Quelldatensatz
uspto-grants-2013_10
Patentnummer
US08562945B2

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