Participants
| Role | Name | HCID | Charge |
|---|
| Reactant | Sodium Carbonate | HCID 10340 | — |
| Reactant | 5-Methoxypyridine-3-boronic Acid | HCID 2763087 | — |
| Reactant | 2-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl | HCID 11155794 | — |
| Reactant | 6-chloro-N-(6-(2-methylpyrrolidin-1-yl)pyridin-2-yl)imidazo[1,2-b]pyridazin-8-amine | HCID 71534384 | — |
| Catalyst | (1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladium | HCID 6505921 | — |
| Solvent | 1,4-Dioxane--water (1/1) | HCID 21886435 | — |
| Product | HCID 71526616 | HCID 71526616 | 49.8% |
Reaction Steps
A mixture of 6-chloro-N-(6-(2-methylpyrrolidin-1-yl)pyridin-2-yl)imidazo[1,2-b]pyridazin-8-amine (0.05 g, 0.15 mmol), 5-methoxypyridin-3-ylboronic acid (0.028 g, 0.18 mmol), Pd(dba)2 (0.02 g, 0.035 mmol), X-Phos (0.02 g, 0.042 mmol) and Na2CO3 (0.032 g, 0.3 mmol) in dioxane/H2O (20 mL/2 mL) was stirred at 95° C. for 18 h under N2 atmosphere. The solvent was removed in vacuo and the residue purified by chromatography (silica gel, petroleum ether/ethyl acetate 3:1) to give 6-(5-methoxypyridin-3-yl)-N-(6-(2-methylpyrrolidin-1-yl)pyridin-2-yl)imidazo[1,2-b]pyridazin-8-amine (0.03 g, 49%) as a yellow solid. 1H NMR (300 MHz, CD3OD): δ 8.28 (s, 1H), 8.72 (s, 1H), 8.40 (s, 1H), 8.12 (s, 1H), 7.98 (s, 1H), 7.72 (s, 1H), 7.49 (t, 1H, J=7.9 Hz), 6.34 (d, 1H, J=7.8 Hz), 6.17 (d, 1H, J=7.8 Hz), 4.31-4.27 (m, 1H), 4.01 (s, 3H), 3.68-3.63 (m, 1H), 3.51-3.43 (m, 1H), 2.20-2.07 (m, 3H), 1.81 (brs, 1H), 1.23 (d, 3H, J=6.0 Hz). LC/MS: 402 [M+H]+, tR=1.73 min. HPLC: 99.91% at 214 nm, 99.92% at 254 nm, tR=5.59 min.
Provenance & Evidence
| DOI | 10.6084/m9.figshare.5104873.v1 |
|---|
| Patent number | US09169259B2 |
|---|
| Source dataset | uspto-grants-2015_10 |
|---|
| ORD ID | ord-9107b9b5d7aa4cad8a85d4dbd7b0ebfc |
|---|
| Source note | uspto-grants-2015_10 |
|---|
