2-Amino-5-fluoro-N-methoxy-N-methylbenzamide → (2-Amino-5-fluorophenyl)(pyridin-2-yl)methanone

HRID 1616060

Reaktionsgleichung

Reaktionsgleichung von HRID 1616060
[NH2:1][C:2]1[CH:13]=[CH:12][C:11]([F:14])=[CH:10][C:3]=1[C:4](N(OC)C)=[O:5].C([Mg]Cl)(C)C.[N:20]1[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=1[Mg]Br>C1COCC1.C(Cl)Cl>[NH2:1][C:2]1[CH:13]=[CH:12][C:11]([F:14])=[CH:10][C:3]=1[C:4]([C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][N:20]=1)=[O:5]

Komponenten

6

Edukt 3

HCID 534075722-Amino-5-fluoro-N-methoxy-N-methylbenzamideHCID 178418918HCID 178418918, VerbindungHCID 178419629HCID 178419629, Verbindung

Produkt 1

HCID 69673534(2-Amino-5-fluorophenyl)(pyridin-2-yl)methanone

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6344DichloromethaneLösungsmittelHCID 8028TetrahydrofuranLösungsmittel3×

Versuchsvorschrift

To a −78° C. solution of 2-amino-5-fluoro-N-methoxy-N-methylbenzamide (9.40 g, 47.4 mmol) in THF (39.5 mL) was added isopropylmagnesium chloride 2.0M in THF (47.4 mL, 94.8 mmol) at −40° C. The solution was allowed to rise to −10° C. over 40 min then was lowered back to −40° C. in an acetonitrile/dry ice bath. To the cooled mixture was added 2-pyridylmagnesium bromide, 0.25M in THF (209 mL, 52.2 mmol) and the mixture was allowed to warm to rt. After 22 h, the reaction was diluted with DCM (200 mL) and quenched with satd ammonium chloride solution (200 mL). The aq layer was extracted with DCM (2×100 mL). The organic extract was dried over Na2SO4. The solution was filtered and concentrated in vacuo. The crude material was purified by silica gel column chromatography eluting with a gradient of 0% to 100% EtOAc in hexane, to provide (2-amino-5-fluorophenyl)(pyridin-2-yl)methanone as orange solid: 1H NMR (400 MHz, DMSO-d6) δ ppm 8.65-8.72 (1H, m), 8.02 (1H, td, J=7.7, 1.8 Hz), 7.79 (1H, dt, J=7.8, 1.0 Hz), 7.60 (1H, ddd, J=7.6, 4.9, 1.2 Hz), 7.29-7.36 (1H, m), 7.18-7.29 (3H, m), 6.88 (1H, dd, J=9.2, 4.7 Hz); LC-MS (ESI) m/z 217.0 [M+H]+.

Aufarbeitung

  1. customthen was lowered back to −40° C. in an acetonitrile/dry ice bath
  2. waitAfter 22 h
  3. customquenched with satd ammonium chloride solution (200 mL)
  4. extractionThe aq layer was extracted with DCM (2×100 mL)
  5. extractionThe organic extract
  6. dry with materialwas dried over Na2SO4
  7. filtrationThe solution was filtered
  8. concentrationconcentrated in vacuo
  9. customThe crude material was purified by silica gel column chromatography
  10. washeluting with a gradient of 0% to 100% EtOAc in hexane

Quellen und Nachweise

ORD-Eintrag
ord-ab602d6d07404defb643f069e86117be
Quelldatensatz
uspto-grants-2014_07
Patentnummer
US08765768B2

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