Cesium carbonate → 2-(2-chloro-5-fluoropyridin-4-ylamino)-N-methylbenzamide

HRID 1045936Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1045936
C(=O)([O-])[O-].[Cs+].[Cs+].[NH2:7][C:8]1[CH:17]=[CH:16][CH:15]=[CH:14][C:9]=1[C:10]([NH:12][CH3:13])=[O:11].[Cl:18][C:19]1[CH:24]=[C:23](I)[C:22]([F:26])=[CH:21][N:20]=1>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1>[Cl:18][C:19]1[CH:24]=[C:23]([NH:7][C:8]2[CH:17]=[CH:16][CH:15]=[CH:14][C:9]=2[C:10]([NH:12][CH3:13])=[O:11])[C:22]([F:26])=[CH:21][N:20]=1

Komponenten

7

Edukt 3

HCID 10796Cesium carbonateHCID 3080722-Amino-N-methylbenzamideHCID 248204952-Chloro-5-fluoro-4-iodopyridine

Produkt 1

HCID 596201352-(2-chloro-5-fluoropyridin-4-ylamino)-N-methylbenzamideAusbeute 83 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 167845palladium(II) acetateKatalysatorHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)KatalysatorHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

Cesium carbonate (651 mg, 2.00 mmol) was added to a mixture of 2-amino-N-methylbenzamide (150 mg, 1.00 mmol), 2-chloro-5-fluoro-4-iodopyridine (257 mg, 1.00 mmol), 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (35 mg, 0.06 mmol) and palladium(II) acetate (9 mg, 0.04 mmol) in dioxane (10 mL) under an atmosphere of nitrogen and the resulting suspension was heated at 80° C. for 24 hours. The mixture was filtered through Celite and the residue washed with CH2Cl2 (20 mL). The filtrate was evaporated and the residue was then dissolved in CH2Cl2 (40 mL) and washed sequentially with a saturated solution of NaHCO3 (25 mL), water (25 mL), and finally with a saturated solution of NaCl (25 mL). The organic layer was dried over MgSO4 and then evaporated to leave a solid. The solid was triturated in CH2Cl2 to afford 2-(2-chloro-5-fluoropyridin-4-ylamino)-N-methylbenzamide (231 mg, 83% yield); 1H NMR spectrum (300.132 MHz, d6 DMSO+d4 Acetic acid): δ 2.76 (3H, s), 7.19 (1H, m), 7.22 (1H, d), 7.50-7.58 (2H, m), 7.71 (1H, dd), 8.19 (1H, d); Mass spectrum: m/z (ESI+) (M+H)+=280.0 and 282.0.

Aufarbeitung

  1. filtrationThe mixture was filtered through Celite
  2. washthe residue washed with CH2Cl2 (20 mL)
  3. customThe filtrate was evaporated
  4. dissolutionthe residue was then dissolved in CH2Cl2 (40 mL)
  5. washwashed sequentially with a saturated solution of NaHCO3 (25 mL), water (25 mL)
  6. dry with materialThe organic layer was dried over MgSO4
  7. customevaporated
  8. customto leave a solid
  9. customThe solid was triturated in CH2Cl2

Quellen und Nachweise

ORD-Eintrag
ord-e750ef28b3f04adc9657fbdd73124de8
Quelldatensatz
uspto-grants-2013_10
Patentnummer
US08569298B2

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