1-Methyl-3-aminopyrazole → HCID 25261179, compound

HRID 1966228Notes

Reaction equation

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

Participants

Conditions

Temperature: 80 °C

Procedure

2-Bromo-5-propoxy-pyridine (0.96 mmol), sodium-tert.-butylate (1.4 eq.), and 1-methyl-1H-pyrazole-3-amine (1.3 eq.) are dissolved in degassed dioxane (2 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 60 min to 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. (1-Methyl-1H-pyrazole-3-yl)-(5-propoxy-pyridine-2-yl)-amine (“A23”) is obtained after reversed phase column chromatography (water/acetonitrile+0.1% TFA) as a colorless powder in a yield of 43%; HPLC (method C): 1.41 min; LC-MS (method A): 0.81 min, 233.0 (M+H+); 1H-NMR (DMSO-d6, 400 MHz): δ [ppm] 10.651 (s, 1H), 7.869 (d, 1H, J=2.9 Hz), 7.747-7.710 (m, 2H), 7.299 (d, 1H, J=9.6 Hz), 6.099 (d, 1H, J=2.3 Hz), 3.949 (t, 2H, J=6.4 Hz), 3.841 (s, 3H), 1.785-1.697 (m, 2H), 3.323 (t, 3H, J=7.4 Hz).

Workup

temperaturethe reaction mixture is heated for 60 min to 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-f207c221c03c4b61b23c407e22bb6512
Source dataset: uspto-grants-2013_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08420642B2

Reaction notes

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