Ammonium Chloride → N-(5-(3-(4-amino-6-methyl-1,3,5-triazin-2-yl)-5-methoxypyridin-2-ylamino)-2-chloropyridin-3-yl)methanesulfonamide

HRID 1621945

Reaktionsgleichung

Reaktionsgleichung von HRID 1621945
F[C:2]1[C:7]([C:8]2[N:13]=[C:12]([CH3:14])[N:11]=[C:10]([NH2:15])[N:9]=2)=[CH:6][C:5]([O:16][CH3:17])=[CH:4][N:3]=1.[NH2:18][C:19]1[CH:20]=[C:21]([NH:26][S:27]([CH3:30])(=[O:29])=[O:28])[C:22]([Cl:25])=[N:23][CH:24]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Na+].[NH4+].[Cl-]>CN(C=O)C>[NH2:15][C:10]1[N:11]=[C:12]([CH3:14])[N:13]=[C:8]([C:7]2[C:2]([NH:18][C:19]3[CH:20]=[C:21]([NH:26][S:27]([CH3:30])(=[O:29])=[O:28])[C:22]([Cl:25])=[N:23][CH:24]=3)=[N:3][CH:4]=[C:5]([O:16][CH3:17])[CH:6]=2)[N:9]=1

Komponenten

6

Edukt 4

HCID 25517Ammonium ChlorideHCID 2724254Sodium bis(trimethylsilyl)amideHCID 666111694-(2-Fluoro-5-methoxypyridin-3-yl)-6-methyl-1,3,5-triazin-2-amineHCID 71480920N-(5-amino-2-chloro-3-pyridinyl)methanesulfonamide

Produkt 1

HCID 59548335N-(5-(3-(4-amino-6-methyl-1,3,5-triazin-2-yl)-5-methoxypyridin-2-ylamino)-2-chloropyridin-3-yl)methanesulfonamideAusbeute 14,3 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

To a 5 mL microwave vial, 4-(2-fluoro-5-methoxypyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine (0.0550 g, 0.234 mmol) and N-(5-amino-2-chloropyridin-3-yl)methanesulfonamide (Step 2, 0.0579 g, 0.261 mmol) were dissolved into DMF (1 mL). NaHMDS (Aldrich, 1 M in THF, 0.935 mL, 0.935 mmol) was added slowly at 0° C. and the dark red mixture was stirred at that temperature for 40 min. The mixture was poured into sat'd NH4Cl (20 mL) and stirred for 5 min. The resulting solid was collected via filtration, washed with water and purified by preparative HPLC using a Phenomenex Gemni 5 micron C18 100×30 mm column (1%-90% CH3CN w/0.1% TFA/H2O w/0.1% TFA in 10 min). The fractions were combined and concentrated. The residue was taken into sat'd NaHCO3. The aqueous pH was adjusted to pH 4-5 and the resulting solid was collected to give N-(5-(3-(4-amino-6-methyl-1,3,5-triazin-2-yl)-5-methoxypyridin-2-ylamino)-2-chloropyridin-3-yl)methanesulfonamide (0.0146 g, 14% yield) as a yellow solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 11.97 (br. s., 1H) 9.62 (br. s., 1H) 8.61 (d, J=14.08 Hz, 2H) 8.41 (br. s., 1H) 8.20 (br. s., 1H) 7.68-8.09 (m, 2H) 3.86 (br. s., 3H) 3.13 (br. s., 3H) 2.45 (br. s., 3H). m/z (ESI, positive ion) m/z: 436.9 (M+H)+.

Aufarbeitung

  1. stirringstirred for 5 min
  2. filtrationThe resulting solid was collected via filtration
  3. washwashed with water
  4. custompurified by preparative HPLC
  5. customC18 100×30 mm column (1%-90% CH3CN w/0.1% TFA/H2O w/0.1% TFA in 10 min)
  6. concentrationconcentrated
  7. customthe resulting solid was collected

Quellen und Nachweise

ORD-Eintrag
ord-caa7f882fa6647788bf1df04299d2807
Quelldatensatz
uspto-grants-2014_07
Patentnummer
US08772480B2

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