Cesium carbonate → 6-bromo-N-(4-(1-(4-methoxybenzyl)-1H-1,2,3-triazol-4-yl)pyridin-2-yl)-4-methylpyridin-2-amine

HRID 2402378Notes

Reaction equation

HRID 2402378 reaction equation
Br[C:2]1[CH:7]=[C:6]([C:8]2[N:9]=[N:10][N:11]([CH2:13][C:14]3[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=3)[CH:12]=2)[CH:5]=[CH:4][N:3]=1.[Br:22][C:23]1[CH:28]=[C:27]([CH3:29])[CH:26]=[C:25]([NH2:30])[N:24]=1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C([O-])([O-])=O.[Cs+].[Cs+]>CC([O-])=O.CC([O-])=O.[Pd+2]>[Br:22][C:23]1[N:24]=[C:25]([NH:30][C:2]2[CH:7]=[C:6]([C:8]3[N:9]=[N:10][N:11]([CH2:13][C:14]4[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=4)[CH:12]=3)[CH:5]=[CH:4][N:3]=2)[CH:26]=[C:27]([CH3:29])[CH:28]=1

Participants

6

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 221765076-Bromo-4-methylpyridin-2-amineHCID 866808002-bromo-4-(1-(4-methoxybenzyl)-1H-1,2,3-triazol-4-yl)pyridine

Product 1

HCID 866808016-bromo-N-(4-(1-(4-methoxybenzyl)-1H-1,2,3-triazol-4-yl)pyridin-2-yl)-4-methylpyridin-2-amineYield 59.3%

Reagents, catalysts & solvents 1

HCID 167845palladium(II) acetateCatalyst

Conditions

Temperature
100 °C

Procedure

To a flask was added 2-bromo-4-(1-(4-methoxybenzyl)-1H-1,2,3-triazol-4-yl)pyridine (329 mg, 0.953 mmol), 2-bromo-4-methyl-6-aminopyridine (178 mg, 0.953 mmol), Pd(OAc)2 (21.4 mg, 0.095 mmol), Xantphos (83 mg, 0.143 mmol), and Cs2CO3 (621 mg, 1.91 mmol), and the mixture was vacuum-purged with argon 3 times. Degassed 1,4-Dioxane (3.8 mL) was added and the reaction was heated to 100° C. for 30 min. after which time the reaction was cooled and diluted with EtOAc (20 mL). The reaction was filtered then dry loaded onto silica and purified by silica gel chromatography using a gradient solvent system of 30-60% EtOAc/Hexanes. Concentration of the product-containing fractions yielded 6-bromo-N-(4-(1-(4-methoxybenzyl)-1H-1,2,3-triazol-4-yl)pyridin-2-yl)-4-methylpyridin-2-amine (255 mg, 59%) as a tan solid. MS ESI calcd for C21H19BrN6O [M+H]+ 451, found 451.

Workup

  1. customthe mixture was vacuum-purged with argon 3 times
  2. additionDegassed 1,4-Dioxane (3.8 mL) was added
  3. temperaturewas cooled
  4. additiondiluted with EtOAc (20 mL)
  5. filtrationThe reaction was filtered
  6. customthen dry
  7. custompurified by silica gel chromatography

Sources & evidence

ORD record
ord-e15f7cd93ecc4f449b59e1b9c96fdac9
Source dataset
uspto-grants-2014_08
Patent number
US08796310B2

Reaction notes

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