Potassium Carbonate → 3-[5-(Azetidine-1-carbonyl)-3-chloro-pyridin-2-yl]oxy-5-[(3S)-1-methyl-2-oxo-pyrrolidin-3-yl]oxy-N-(5-methylpyrazin-2-yl)benzamide

HRID 600513Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 600513
[OH:1][C:2]1[CH:3]=[C:4]([CH:15]=[C:16]([O:18][C@H:19]2[CH2:23][CH2:22][N:21]([CH3:24])[C:20]2=[O:25])[CH:17]=1)[C:5]([NH:7][C:8]1[CH:13]=[N:12][C:11]([CH3:14])=[CH:10][N:9]=1)=[O:6].[N:26]1([C:30]([C:32]2[CH:33]=[N:34][C:35](Cl)=[C:36]([Cl:38])[CH:37]=2)=[O:31])[CH2:29][CH2:28][CH2:27]1.C(=O)([O-])[O-].[K+].[K+]>CC(N(C)C)=O>[N:26]1([C:30]([C:32]2[CH:37]=[C:36]([Cl:38])[C:35]([O:1][C:2]3[CH:3]=[C:4]([CH:15]=[C:16]([O:18][C@H:19]4[CH2:23][CH2:22][N:21]([CH3:24])[C:20]4=[O:25])[CH:17]=3)[C:5]([NH:7][C:8]3[CH:13]=[N:12][C:11]([CH3:14])=[CH:10][N:9]=3)=[O:6])=[N:34][CH:33]=2)=[O:31])[CH2:29][CH2:28][CH2:27]1

Komponenten

5

Edukt 3

HCID 11430Potassium CarbonateHCID 536296165-(Azetidin-1-ylcarbonyl)-2,3-dichloropyridine2×HCID 597611393-hydroxy-5-[(3S)-1-methyl-2-oxo-pyrrolidin-3-yl]oxy-N-(5-methylpyrazin-2-yl)benzamide2×

Produkt 1

HCID 249523033-[5-(Azetidine-1-carbonyl)-3-chloro-pyridin-2-yl]oxy-5-[(3S)-1-methyl-2-oxo-pyrrolidin-3-yl]oxy-N-(5-methylpyrazin-2-yl)benzamideAusbeute 87,5 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 31374DimethylacetamideLösungsmittel

Reaktionsbedingungen

Temperatur
120 °C

Versuchsvorschrift

A mixture of 3-hydroxy-5-[(3S)-1-methyl-2-oxo-pyrrolidin-3-yl]oxy-N-(5-methylpyrazin-2-yl)benzamide (Intermediate 18) (136 mg, 0.4 mmol), azetidin-1-yl-(5,6-dichloropyridin-3-yl)methanone (Intermediate 21) (103 mg, 0.44 mmol) and potassium carbonate (111 mg, 0.8 mmol) in DMA (5 mL) was stirred at 120° C. for 2 hours. The solution was evaporated under reduced pressure, the residue dissolved in ethyl acetate (40 mL) washed with water (2×20 mL), brine (20 mL), dried (MgSO4), filtered and the solvent removed under reduced pressure. The residue was purified by flash chromatography on silica, eluting with a gradient of 0-4% methanol in DCM to afford the product (188 mg, 87%). 1H NMR δ (300 MHz, CDCl3) 2.16-2.29 (m, 1H), 2.40 (quintet, 2H), 2.50-2.72 (m, 4H), 2.95 (s, 3H), 3.36-3.58 (m, 2H), 4.18-4.42 (m, 4H), 4.95 (t, 1H), 7.15 (s, 1H), 7.37 (s, 1H), 7.55 (s, 1H), 8.15 (s, 2H), 8.25 (s, 1H), 8.55 (s, 1H), 9.54 (s, 1H); m/z 537 (M+H)+.

Aufarbeitung

  1. customThe solution was evaporated under reduced pressure
  2. dissolutionthe residue dissolved in ethyl acetate (40 mL)
  3. washwashed with water (2×20 mL), brine (20 mL)
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. customthe solvent removed under reduced pressure
  7. customThe residue was purified by flash chromatography on silica
  8. washeluting with a gradient of 0-4% methanol in DCM

Quellen und Nachweise

ORD-Eintrag
ord-862f2fd5ec2149678d2803563db0ac67
Quelldatensatz
uspto-grants-2011_03
Patentnummer
US07902200B2

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