Sodium Carbonate → (S)-3-((S)-1-(4-(1-cyclopropyl-2-oxo-1,2-dihydropyridin-4-yl)phenyl)ethyl)-7-(2-hydroxy-2-methylpropyl)-7-phenyl-1,3-oxazepan-2-one

HRID 219632Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 219632
[OH:1][C:2]([CH3:36])([CH3:35])[CH2:3][C@@:4]1([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[O:10][C:9](=[O:11])[N:8]([C@H:12]([C:14]2[CH:19]=[CH:18][C:17](B3OC(C)(C)C(C)(C)O3)=[CH:16][CH:15]=2)[CH3:13])[CH2:7][CH2:6][CH2:5]1.[CH:37]1([N:40]2[CH:45]=[CH:44][C:43](I)=[CH:42][C:41]2=[O:47])[CH2:39][CH2:38]1.C([O-])([O-])=O.[Na+].[Na+]>C1(C)C=CC=CC=1.CCO.O.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH:37]1([N:40]2[CH:45]=[CH:44][C:43]([C:17]3[CH:18]=[CH:19][C:14]([C@@H:12]([N:8]4[CH2:7][CH2:6][CH2:5][C@:4]([CH2:3][C:2]([OH:1])([CH3:36])[CH3:35])([C:29]5[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=5)[O:10][C:9]4=[O:11])[CH3:13])=[CH:15][CH:16]=3)=[CH:42][C:41]2=[O:47])[CH2:39][CH2:38]1

Komponenten

7

Edukt 3

HCID 10340Sodium CarbonateHCID 59190368(S)-7-(2-hydroxy-2-methylpropyl)-7-phenyl-3-((S)-1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)ethyl)-1,3-oxazepan-2-oneHCID 591903761-cyclopropyl-4-iodopyridin-2(1H)-one

Produkt 1

HCID 59190394(S)-3-((S)-1-(4-(1-cyclopropyl-2-oxo-1,2-dihydropyridin-4-yl)phenyl)ethyl)-7-(2-hydroxy-2-methylpropyl)-7-phenyl-1,3-oxazepan-2-oneAusbeute 40 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 962WaterLösungsmittelHCID 86587398Ethanol toluene waterLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

A mixture of (S)-7-(2-hydroxy-2-methylpropyl)-7-phenyl-3-((S)-1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)ethyl)-1,3-oxazepan-2-one (20 mg, 0.04 mmol), 1-cyclopropyl-4-iodopyridin-2(1H)-one (10 mg, 0.04 mmol), Pd(PPh3)4 (5 mg), and Na2CO3 (43 mg, 0.36 mmol) in toluene/EtOH/H2O (3 mL/2 mL/2 mL) was stirred under N2 at 100° C. for 2 h. The reaction mixture was diluted with water (5 mL), and extracted with EtOAc. The combined organic layers were washed with brine, dried over Na2SO4, and concentrated to give the crude product, which was purified by preparative-HPLC to give (S)-3-((S)-1-(4-(1-cyclopropyl-2-oxo-1,2-dihydropyridin-4-yl)phenyl)ethyl)-7-(2-hydroxy-2-methylpropyl)-7-phenyl-1,3-oxazepan-2-one (8 mg, yield 40%) LC-MS Method 4 tR=1.166 min, m/z=443.1; 1H NMR (CDCl3) d 0.85 (m, 5H), 1.10 (m, 6H), 1.43 (m, 1H), 1.52 (d, 3H), 2.18 (m, 2H), 2.20 (d, 1H), 2.36 (d, 1H), 2.79 (m, 1H), 3.12-3.35 (m, 2H), 4.00 (s, 1H), 5.59 (m, 1H), 6.30 (d, 1H), 6.70 (d, 1H), 7.18-7.32 (m, 6H), 7.45 (m, 4H)

Aufarbeitung

  1. extractionextracted with EtOAc
  2. washThe combined organic layers were washed with brine
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated
  5. customto give the crude product, which
  6. customwas purified by preparative-HPLC

Quellen und Nachweise

ORD-Eintrag
ord-ad5246ce427c4226894cc924303ff2c5
Quelldatensatz
uspto-grants-2012_06
Patentnummer
US08202857B2

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