4-Bromo-2-methylpyridine → 8-(3-methoxyphenyl)-N-(2-methylpyridin-4-yl)-[1,2,4]triazolo[1,5-a]pyridin-2-amine

HRID 57768

Reaktionsgleichung

Reaktionsgleichung von HRID 57768
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:9]2[C:10]3[N:11]([N:15]=[C:16]([NH2:18])[N:17]=3)[CH:12]=[CH:13][CH:14]=2)[CH:6]=[CH:7][CH:8]=1.Br[C:20]1[CH:25]=[CH:24][N:23]=[C:22]([CH3:26])[CH:21]=1.CC(C)([O-])C.[Na+].C1(P(C2C=C(C)C=C(C)C=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=C(C)C=C(C)C=2)C2C=C(C)C=C(C)C=2)C=C(C)C=C(C)C=1>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:9]2[C:10]3[N:11]([N:15]=[C:16]([NH:18][C:20]4[CH:25]=[CH:24][N:23]=[C:22]([CH3:26])[CH:21]=4)[N:17]=3)[CH:12]=[CH:13][CH:14]=2)[CH:6]=[CH:7][CH:8]=1

Komponenten

7

Edukt 4

HCID 27628354-Bromo-2-methylpyridineHCID 4189905(R)-(+)-2,2'-Bis(di(3,5-xylyl)phosphino)-1,1'-binaphthylHCID 23676156Sodium t-butoxideHCID 591991028-(3-Methoxyphenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-ylamine

Produkt 1

HCID 445543178-(3-methoxyphenyl)-N-(2-methylpyridin-4-yl)-[1,2,4]triazolo[1,5-a]pyridin-2-amineAusbeute 39 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 1140TolueneLösungsmittel

Reaktionsbedingungen

Temperatur
110 °C

Versuchsvorschrift

A suspension of 8-(3-methoxyphenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-amine (0.150 g, 0.625 mmol, 1 equiv), 4-bromo-2-methylpyridine (0.160 g, 0.935 mmol, 1.5 equiv), tris(dibenzylideneacetone)dipalladium (0) (27.5 mg, 0.03 mmol, 0.05 equiv), sodium tert-butoxide (0.90 g, 0.94 mmol, 1.5 equiv), and 2,2′-bis[di(3,5-xylyl)phosphino]-1,1′-binaphthyl (38.9 mg, 0.625 mmol, 0.1 equiv) in toluene (2 mL) was purged with nitrogen for 15 min. The reaction mixture was heated at 110° C. by microwave for 10 min. The reaction mixture was diluted with ethyl acetate (50 mL) and filtered through celite. The filtrate was then washed with brine (3×20 mL), dried over anhydrous sodium sulfate, filtered, and concentrated. Purification by preparative HPLC afforded 8-(3-methoxyphenyl)-N-(2-methylpyridin-4-yl)-[1,2,4]triazolo[1,5-a]pyridin-2-amine (80 mg, 39%). LCMS (ESI) m/z: 332.1; 1H NMR (400 MHz, DMSO-d6) δ: 10.45 (br s, 1H), 8.81 (dd, J=6.4, 0.8 Hz, 1H), 8.23 (d, J=6.0 Hz, 1H), 7.88 (dd, J=6.8, 0.8 Hz, 1H), 7.74 (s, 1H), 7.64 (d, J=8.0 Hz, 1H), 7.57 (s, 1H), 7.54 (dd, J=6.0, 2.0 Hz, 1H), 7.41 (t, J=8.0 Hz, 1H), 7.15 (t, J=6.8 Hz, 1H), 7.00 (dd, J=8.0, 2.4 Hz, 1H), 3.83 (s, 3H), 2.42 (s, 3H).

Aufarbeitung

  1. customwas purged with nitrogen for 15 min
  2. additionThe reaction mixture was diluted with ethyl acetate (50 mL)
  3. filtrationfiltered through celite
  4. washThe filtrate was then washed with brine (3×20 mL)
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification by preparative HPLC

Quellen und Nachweise

ORD-Eintrag
ord-b476c94d77f24336978f0fd1e5a28383
Quelldatensatz
uspto-grants-2016_09
Patentnummer
US09434732B2

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