Diisopropyl azodicarboxylate → tert-Butyl (3S)-3-[4-({3-[4-(phenylcarbonyl)piperazin-1-yl]azetidin-1-yl}carbonyl)phenoxy]pyrrolidine-1-carboxylate

HRID 1911148Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1911148
[C:1]1([C:7]([N:9]2[CH2:14][CH2:13][N:12]([CH:15]3[CH2:18][N:17]([C:19]([C:21]4[CH:26]=[CH:25][C:24]([OH:27])=[CH:23][CH:22]=4)=[O:20])[CH2:16]3)[CH2:11][CH2:10]2)=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:28]([N:35]1[CH2:42][CH2:41][CH:40](O)[C@@H:36]1C(O)=O)([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29].CC(OC(/N=N/C(OC(C)C)=O)=O)C>C1COCC1>[C:1]1([C:7]([N:9]2[CH2:14][CH2:13][N:12]([CH:15]3[CH2:18][N:17]([C:19]([C:21]4[CH:22]=[CH:23][C:24]([O:27][C@H:41]5[CH2:40][CH2:36][N:35]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH2:42]5)=[CH:25][CH:26]=4)=[O:20])[CH2:16]3)[CH2:11][CH2:10]2)=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Komponenten

5

Edukt 3

HCID 5363146Diisopropyl azodicarboxylateHCID 20609990(R)-N-Boc-3-hydroxyprolineHCID 596258104-({3-[4-(Phenylcarbonyl)piperazin-1-yl]azetidin-1-yl}carbonyl)phenol

Produkt 1

HCID 59625931tert-Butyl (3S)-3-[4-({3-[4-(phenylcarbonyl)piperazin-1-yl]azetidin-1-yl}carbonyl)phenoxy]pyrrolidine-1-carboxylate

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

To a solution of compound 26d (100 mg, 0.273 mmol) and (R)—N-Boc-3-hydroxyproline in THF was added DIAD at 0° C. The resulting reaction mixture was stirred for 18 h. After dilution with water and extraction with EtOAc (3×), the combined organic extracts were dried over Na2SO4, filtered, and concentrated under reduced pressure. The resultant residue was purified by flash column chromatography on silica gel using 5% MeOH/CH2Cl2 to give compound 434 (95 mg). 1H NMR (CDCl3): δ 7.52 (d, J=8.6 Hz, 2H), 7.37-7.44 (m, 5H), 7.24-7.29 (m, 3H), 7.18-7.24 (m, 3H), 4.18-4.33 (m, 2H), 4.09-4.17 (m, 3H), 4.01-4.08 (m, 1H), 3.92 (br. S, 1H), 3.74 (br. s., 1H), 3.35-3.63 (m, 2H), 3.17-3.29 (m, 1H), 2.20-2.50 (m, 4H); MS m/z (M+H+) 506.0.

Aufarbeitung

  1. customThe resulting reaction mixture
  2. extractionAfter dilution with water and extraction with EtOAc (3×)
  3. dry with materialthe combined organic extracts were dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe resultant residue was purified by flash column chromatography on silica gel using 5% MeOH/CH2Cl2

Quellen und Nachweise

ORD-Eintrag
ord-c479ea3a71134369a7c6b2a26653b2d7
Quelldatensatz
uspto-grants-2013_12
Patentnummer
US08604017B2

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