Sodium Carbonate → HCID 71526079, compound

HRID 1755362Notes

Reaction equation

HRID 1755362 reaction equation
Cl[C:2]1[CH:3]=[C:4]([NH:11][C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([N:18]3[CH2:22][CH2:21][CH2:20][CH:19]3[CH3:23])[N:13]=2)[C:5]2[N:6]([CH:8]=[CH:9][N:10]=2)[N:7]=1.[C:24]1([CH3:33])[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=1B(O)O.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.O.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]>[CH3:23][CH:19]1[CH2:20][CH2:21][CH2:22][N:18]1[C:14]1[N:13]=[C:12]([NH:11][C:4]2[C:5]3[N:6]([CH:8]=[CH:9][N:10]=3)[N:7]=[C:2]([C:25]3[CH:26]=[CH:27][CH:28]=[CH:29][C:24]=3[CH3:33])[CH:3]=2)[CH:17]=[CH:16][CH:15]=1

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 27332672-Methylphenyl boronic acidHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 715343846-chloro-N-(6-(2-methylpyrrolidin-1-yl)pyridin-2-yl)imidazo[1,2-b]pyridazin-8-amine

Product 1

HCID 71526079HCID 71526079, compoundYield 44%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 6-chloro-N-(6-(2-methylpyrrolidin-1-yl)pyridin-2-yl)imidazo[1,2-b]pyridazin-8-amine (0.10 g, 0.304 mmol), o-tolylboronic acid (0.045 g, 0.335 mmol), Pd2(dba)3 (0.017 g, 0.03 mmol), X-phos (0.029 g, 0.06 mmol) and Na2CO3 (0.097 g, 0.912 mmol) in dioxane (20 mL) and water (5 mL) was heated to 100° C. for 16 h in a sealed tube under N2 atmosphere then concentrated in vacuo. The residue was purified by chromatography (silica gel, 10 g, 200˜300 mesh, ethyl acetate:petroleum ether=1:15) to afford N-(6-(2-methylpyrrolidin-1-yl)pyridin-2-yl)-6-o-tolylimidazo[1,2-b]pyridazin-8-amine (51 mg, 44%) as a yellow solid. 1H NMR (300 MHz, CD3OD): δ 8.53 (s, 1H), 7.95 (s, 1H), 7.61 (s, 1H), 7.43-7.25 (m, 5H), 6.28 (d, 1H, J=7.5 Hz), 6.02 (d, 1H, J=8.1 Hz), 4.10-4.06 (m, 1H), 3.55 (s, 1H), 3.45-3.39 (m, 1H), 3.24-3.21 (m, 1H), 2.37 (s, 3H), 2.03-1.89 (m, 3H), 1.61-1.58 (m, 1H), 0.97 (d, 3H, J=6.3 Hz). LC-MS: [M+H]+, 385, tR=1.95 min, HPLC: 99.76% at 214 nm, 100% at 254 nm, tR=4.68 min.

Workup

  1. concentrationthen concentrated in vacuo
  2. customThe residue was purified by chromatography (silica gel, 10 g, 200˜300 mesh, ethyl acetate:petroleum ether=1:15)

Sources & evidence

ORD record
ord-b014dd8a5fd448e58871bcfd725432d9
Source dataset
uspto-grants-2015_10
Patent number
US09169259B2

Reaction notes

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