1-Methyl-3-aminopyrazole → (5-Isobutoxy-pyridine-2-yl)-(1-methyl-1H-pyrazole-3-yl)amine

HRID 1966234Notes

Reaction equation

Br[C:2]1[CH:7]=[CH:6][C:5]([O:8][CH2:9][CH:10]([CH3:12])[CH3:11])=[CH:4][N:3]=1.[CH3:13][N:14]1[CH:18]=[CH:17][C:16]([NH2:19])=[N:15]1>O1CCOCC1.Cl[Pd-](P(C1CC2CC1CC2)C1CC2CC1CC2)[C-]1C=CC=C1N(C)C.[CH-]1C=CC=C1.[Fe+2]>[CH2:9]([O:8][C:5]1[CH:6]=[CH:7][C:2]([NH:19][C:16]2[CH:17]=[CH:18][N:14]([CH3:13])[N:15]=2)=[N:3][CH:4]=1)[CH:10]([CH3:12])[CH3:11]

Participants

Conditions

Temperature: 80 °C

Procedure

2-Bromo-5-isobutoxy-pyridine (0.38 mmol), sodium-tert.-butylate (1.4 eq.), and 1-methyl-1H-pyrazole-3-amine (1.2 eq.) are dissolved in degassed dioxane (2 ml) and heated to 80° C. Chloro-(di-2-norbornylphosphino)(2-dimethylaminoferrocene-1-yl)palladium (II) (3 mg) in degassed dioxane (1 ml) is added and the reaction is heated for 1 hour at 150° C. in the microwave. The reaction is quenched with ethylacetate methanol (30 ml, 9:1) and filtrated over celite. The solvent of the filtrate is removed in vacuo. (5-Isobutoxy-pyridine-2-yl)-(1-methyl-1H-pyrazole-3-yl)amine (“A26”) is obtained after reversed phase column chromatography (water/acetonitrile+0.1% TFA) as colorless powder in a yield of 33%; HPLC (method C): 1.57 min; LC-MS (method A): 0.936 min, 247.15 (M+H+);

Workup

temperaturethe reaction is heated for 1 hour at 150° C. in the microwave
customThe reaction is quenched with ethylacetate methanol (30 ml, 9:1)
filtrationfiltrated over celite
customThe solvent of the filtrate is removed in vacuo

Sources & evidence

ORD record: ord-1a303f097346460d9d09d897c3a4abd5
Source dataset: uspto-grants-2013_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08420642B2

Reaction notes

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