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

HRID 57768

反応式

HRID 57768 の反応式
[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

参加物

7

反応物 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

生成物 1

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

試薬・触媒・溶媒 2

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 1140Toluene溶媒

反応条件

温度
110 °C

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-b476c94d77f24336978f0fd1e5a28383
出典データセット
uspto-grants-2016_09
特許番号
US09434732B2

関連ノート

読み込み中…