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

HRID 1913096

Reaction equation

HRID 1913096 reaction equation
[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

Participants

7

Reactant 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

Product 1

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

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

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, 1 H), 8.81 (dd, J=6.4, 0.8 Hz, 1 H), 8.23 (d, J=6.0 Hz, 1 H), 7.88 (dd, J=6.8, 0.8 Hz, 1 H), 7.74 (s, 1 H), 7.64 (d, J=8.0 Hz, 1 H), 7.57 (s, 1 H), 7.54 (dd, J=6.0, 2.0 Hz, 1 H), 7.41 (t, J=8.0 Hz, 1 H), 7.15 (t, J=6.8 Hz, 1 H), 7.00 (dd, J=8.0, 2.4 Hz, 1 H), 3.83 (s, 3 H), 2.42 (s, 3 H).

Workup

  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

Sources & evidence

ORD record
ord-6cda8dd466944c3cb8261ace6950a349
Source dataset
uspto-grants-2013_12
Patent number
US08609687B2

Linked notes

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