1-Methyl-3-aminopyrazole → HCID 25261183, compound

HRID 1966235Notes

Reaction equation

HRID 1966235 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([O:8][C:9]2[CH:14]=[CH:13][C:12]([S:15]([CH3:18])(=[O:17])=[O:16])=[CH:11][CH:10]=2)=[CH:4][N:3]=1.[CH3:19][N:20]1[CH:24]=[CH:23][C:22]([NH2:25])=[N:21]1>O1CCOCC1.Cl[Pd-](P(C1CC2CC1CC2)C1CC2CC1CC2)[C-]1C=CC=C1N(C)C.[CH-]1C=CC=C1.[Fe+2]>[CH3:18][S:15]([C:12]1[CH:13]=[CH:14][C:9]([O:8][C:5]2[CH:6]=[CH:7][C:2]([NH:25][C:22]3[CH:23]=[CH:24][N:20]([CH3:19])[N:21]=3)=[N:3][CH:4]=2)=[CH:10][CH:11]=1)(=[O:17])=[O:16]

Participants

5

Reactant 2

HCID 1372541-Methyl-3-aminopyrazoleHCID 86644606HCID 86644606, compound

Product 1

HCID 25261183HCID 25261183, compoundYield 55%

Reagents, catalysts & solvents 2

HCID 178482626HCID 178482626, compoundCatalystHCID 312751,4-DioxaneSolvent2×

Conditions

Temperature
80 °C

Procedure

2-Bromo-5-(4-methanesulfonyl-phenoxy)-pyridine (0.47 mmol), sodium-tert.-butylate (1.4 eq.), and 1-methyl-1H-pyrazole-3-amine (1.2 eq.) are dissolved in degassed dioxane (2.5 ml) and heated to 80° C. Chloro(di-2-norbornylphosphino)(2-dimethylaminoferrocene-1-yl)palladium (II) (5.9 mg) in degassed dioxane (1 ml) is added and the reaction mixture is heated for 1 hour at 142° C. in the microwave. The reaction is quenched with ethylacetate (30 ml) and filtrated over celite. The solvent of the filtrate is removed in vacuo [5-(4-Methanesulfonyl-phenoxy)-pyridine-2-yl]-(1-methyl-1H-pyrazole-3-yl)-amine (“A27”) is obtained after reversed phase column chromatography (water/acetonitrile+0.1% TFA) as orange powder in a yield of 55%; HPLC (method C): 1.57 min; LC-MS (method A): 0.787 min, 345.15 (M+H+);

Workup

  1. temperaturethe reaction mixture is heated for 1 hour at 142° C. in the microwave
  2. customThe reaction is quenched with ethylacetate (30 ml)
  3. filtrationfiltrated over celite
  4. customThe solvent of the filtrate is removed in vacuo [5-(4-Methanesulfonyl-phenoxy)-pyridine-2-yl]-(1-methyl-1H-pyrazole-3-yl)-amine (“A27”)
  5. customis obtained after reversed phase column chromatography (water/acetonitrile+0.1% TFA) as orange powder in a yield of 55%
  6. custom1.57 min
  7. custom0.787 min, 345.15 (M+H+)

Sources & evidence

ORD record
ord-0745bec8d1cb4998af06f4655b906f46
Source dataset
uspto-grants-2013_04
Patent number
US08420642B2

Reaction notes

Loading…