Sodium Carbonate → 6-(benzo[d][1,3]dioxol-5-yl)-N-(6-(2-methylpyrrolidin-1-yl)pyridin-2-yl)imidazo[1,2-b]pyridazin-8-amine

HRID 1755318Notes

Reaction equation

HRID 1755318 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.[O:24]1[C:28]2[CH:29]=[CH:30][C:31](B(O)O)=[CH:32][C:27]=2[O:26][CH2:25]1.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]>[O:24]1[C:28]2[CH:29]=[CH:30][C:31]([C:2]3[CH:3]=[C:4]([NH:11][C:12]4[CH:17]=[CH:16][CH:15]=[C:14]([N:18]5[CH2:22][CH2:21][CH2:20][CH:19]5[CH3:23])[N:13]=4)[C:5]4[N:6]([CH:8]=[CH:9][N:10]=4)[N:7]=3)=[CH:32][C:27]=2[O:26][CH2:25]1

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 2734371(2H-1,3-benzodioxol-5-yl)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 715256176-(benzo[d][1,3]dioxol-5-yl)-N-(6-(2-methylpyrrolidin-1-yl)pyridin-2-yl)imidazo[1,2-b]pyridazin-8-amineYield 75%

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 (66 mg, 0.2 mmol), benzo[d][1,3]dioxol-5-ylboronic acid (60 mg, 0.24 mmol), Pd2(dba)3 (12 mg, 0.02 mmol), X-phos (39 mg, 0.08 mmol) and Na2CO3 (64 mg, 0.6 mmol) in dioxane (5 mL) and water (0.5 mL) was heated to 100° C. with stirring for 16 h under N2. The solvent was removed in vacuo and the resulting mixture was purified by chromatography (silica gel, 200-300 mesh, CH2Cl2:MeOH=20:1) to give crude product as a yellow oil, which was then purified by chromatography (silica gel, 200-300 mesh, petroleum ether:ethyl acetate=3:1) to give 6-(benzo[d][1,3]dioxol-5-yl)-N-(6-(2-methylpyrrolidin-1-yl)pyridin-2-yl)imidazo[1,2-b]pyridazin-8-amine (62 mg, 75%) as a yellow solid. 1H NMR (300 MHz, DMSO): δ 9.58 (s, 1H), 8.69 (s, 1H), 8.14 (s, 1H), 7.61 (s, 1H), 7.44-7.39 (m, 3H), 7.06-7.04 (m, 1H), 6.70 (d, 1H, J=7.5 Hz), 6.11 (s, 2H), 6.05 (d, 1H, J=8.1 Hz), 4.27-4.20 (m, 1H), 3.58-3.53 (m, 1H), 3.41-3.36 (m, 1H), 2.07-1.99 (m, 3H), 1.71-1.68 (m, 2H), 1.14 (d, 1H, J=6.0 Hz). LC-MS: [M+H]+, 415, tR=1.965 min, HPLC: 99.31% at 214 nm, 99.64% at 254 nm, tR=6.821 min.

Workup

  1. customThe solvent was removed in vacuo
  2. customthe resulting mixture was purified by chromatography (silica gel, 200-300 mesh, CH2Cl2:MeOH=20:1)
  3. customto give crude product as a yellow oil, which
  4. customwas then purified by chromatography (silica gel, 200-300 mesh, petroleum ether:ethyl acetate=3:1)

Sources & evidence

ORD record
ord-44dd9697058c4d089536c6191e9e4970
Source dataset
uspto-grants-2015_10
Patent number
US09169259B2

Reaction notes

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