Dimethylformamide → (S)-6-(2-Hydroxy-2-methyl-propyl)-3-{(S)-1-[4-(1-methyl-2-oxo-1,2-dihydro-pyridin-4-ylethynyl)-phenyl]ethyl}-6-phenyl-[1,3]oxazinan-2-one

HRID 333909

Reaktionsgleichung

Reaktionsgleichung von HRID 333909
CCN(CC)CC.Br[C:9]1[CH:14]=[CH:13][N:12]([CH3:15])[C:11](=[O:16])[CH:10]=1.[C:17]([C:19]1[CH:24]=[CH:23][C:22]([C@@H:25]([N:27]2[CH2:32][CH2:31][C@:30]([CH2:39][C:40]([OH:43])([CH3:42])[CH3:41])([C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=3)[O:29][C:28]2=[O:44])[CH3:26])=[CH:21][CH:20]=1)#[CH:18].CN(C)C=O>[Cu]I.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O>[OH:43][C:40]([CH3:41])([CH3:42])[CH2:39][C@@:30]1([C:33]2[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=2)[O:29][C:28](=[O:44])[N:27]([C@H:25]([C:22]2[CH:21]=[CH:20][C:19]([C:17]#[C:18][C:9]3[CH:14]=[CH:13][N:12]([CH3:15])[C:11](=[O:16])[CH:10]=3)=[CH:24][CH:23]=2)[CH3:26])[CH2:32][CH2:31]1

Komponenten

8

Edukt 4

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 221323964-Bromo-1-methylpyridin-2(1H)-oneHCID 86670541(S)-3-((S)-1-(4-ethynylphenyl)ethyl)-6-(2-hydroxy-2-methylpropyl)-6-phenyl-1,3-oxazinan-2-one

Produkt 1

HCID 66869817(S)-6-(2-Hydroxy-2-methyl-propyl)-3-{(S)-1-[4-(1-methyl-2-oxo-1,2-dihydro-pyridin-4-ylethynyl)-phenyl]ethyl}-6-phenyl-[1,3]oxazinan-2-one

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)KatalysatorHCID 178418476HCID 178418476, VerbindungKatalysatorHCID 962WaterLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

CuI (68 mg), Pd(PPh3)2Cl2 (125 mg), and NEt3 (0.82 mL) were added successively to a flask charged with a stir bar, 4-bromo-1-methyl-1H-pyridin-2-one (0.38 g), 3-[(S)-1-(4-ethynyl-phenyl)-ethyl]-(S)-6-(2-hydroxy-2-methyl-propyl)-6-phenyl-[1,3]oxazinan-2-one (0.61 g), and N,N-dimethylformamide (3 mL) and kept at room temperature under argon atmosphere. The resulting mixture was heated to 100° C. and stirred at this temperature for 4 h. After cooling the mixture to ambient temperature, water was added and the resulting mixture was extracted with ethyl acetate. The combined organic extracts were washed with water and brine and dried (MgSO4). The solvent was evaporated and the residue was chromatographed on silica gel twice (first chromatography: ethyl acetate/methanol 1:0->4:1; second chromatography: dichloromethane/methanol 19:1->9:1) to afford the title compound as an oil which crystallized from ethyl acetate. Yield: 0.27 g (34% of theory); LC-MS (Method 1): tR=3.41 min; Mass spectrum (ESI+): m/z=485 [M+H]+.

Aufarbeitung

  1. additioncharged with a stir bar
  2. customkept at room temperature under argon atmosphere
  3. temperatureAfter cooling the mixture to ambient temperature
  4. extractionthe resulting mixture was extracted with ethyl acetate
  5. washThe combined organic extracts were washed with water and brine
  6. dry with materialdried (MgSO4)
  7. customThe solvent was evaporated
  8. customthe residue was chromatographed on silica gel twice (first chromatography: ethyl acetate/methanol 1:0->4:1; second chromatography: dichloromethane/methanol 19:1->9:1)

Quellen und Nachweise

ORD-Eintrag
ord-8737c493692d403fb7d6f6ec83060ed2
Quelldatensatz
uspto-grants-2014_11
Patentnummer
US08883778B2

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