Chloroform → 6-Methyl-3-(1-methyl-1H-pyrazol-3-ylamino)-pyridine-2-carboxylic acid (1-methyl-1H-pyrazol-3-yl)-amide

HRID 2219547Notes

Reaction equation

HRID 2219547 reaction equation
[CH3:1][N:2]1[CH:6]=[CH:5][C:4]([NH:7][C:8]([C:10]2[C:15](Br)=[CH:14][CH:13]=[C:12]([CH3:17])[N:11]=2)=[O:9])=[N:3]1.[NH2:18][C:19]1[CH:23]=[CH:22][N:21]([CH3:24])[N:20]=1.C(=O)([O-])[O-].[Cs+].[Cs+].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(Cl)(Cl)Cl>O1CCOCC1.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][N:2]1[CH:6]=[CH:5][C:4]([NH:7][C:8]([C:10]2[C:15]([NH:18][C:19]3[CH:23]=[CH:22][N:21]([CH3:24])[N:20]=3)=[CH:14][CH:13]=[C:12]([CH3:17])[N:11]=2)=[O:9])=[N:3]1

Participants

8

Reactant 5

HCID 6212ChloroformHCID 10796Cesium carbonateHCID 1372541-Methyl-3-aminopyrazoleHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 866075903-Bromo-6-methyl-pyridine-2-carboxylic acid (1-methyl-1H-pyrazol-3-yl)-amide

Product 1

HCID 115078586-Methyl-3-(1-methyl-1H-pyrazol-3-ylamino)-pyridine-2-carboxylic acid (1-methyl-1H-pyrazol-3-yl)-amideYield 17.4%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
130 °C

Procedure

In a 10 ml reaction vessel were dissolved 60 mg (0.203 mmol) 3-Bromo-6-methyl-pyridine-2-carboxylic acid (1-methyl-1H-pyrazol-3-yl)-amide and 25 mg (0.254 mmol, 1.5 equiv.) of 3-Amino-1-methyl-pyrazole in 4 ml of dioxane. Cesium carbonate (93 mg, 0.285 mmol, 1.4 equiv.) were added and argon was bubbled through the suspension for 3 min. Then Xanthphos (39 mg, 0.067 mmol, 0.33 equiv.) and Pd2(dba)3.CHCl3 (21 mg, 0.020 mmol, 0.1 equiv.) were added. The vessel was closed and the mixture was heated overnight at 130° C. To the mixture was added silicagel (5 g) and the mixture was evaporated to dryness in vaccuo. The powder was charged onto a silicagel flash chromatography column and eluted (gradient 100% heptane to 100% ethyl acetate) to yield the title compound as a yellow solid (total 11 mg, 17%), MS (ISP): m/e=312.1 (M+H+).

Workup

  1. customIn a 10 ml reaction vessel
  2. customargon was bubbled through the suspension for 3 min
  3. customThe vessel was closed
  4. additionTo the mixture was added silicagel (5 g)
  5. customthe mixture was evaporated to dryness in vaccuo
  6. additionThe powder was charged onto a silicagel flash chromatography column
  7. washeluted (gradient 100% heptane to 100% ethyl acetate)

Sources & evidence

ORD record
ord-6a1386331e9643f3a286028a60e41c15
Source dataset
uspto-grants-2008_08
Patent number
US07414060B2

Reaction notes

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