Sodium Carbonate → HCID 71525714, compound

HRID 1755334Notes

Reaction equation

HRID 1755334 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][CH:20]([CH3:23])[CH2:19]3)[N:13]=2)[C:5]2[N:6]([CH:8]=[CH:9][N:10]=2)[N:7]=1.[C:24]1(B(O)O)[CH:29]=[CH:28][CH:27]=[CH:26][CH: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]>[CH3:23][CH:20]1[CH2:21][CH2:22][N:18]([C:14]2[N:13]=[C:12]([NH:11][C:4]3[C:5]4[N:6]([CH:8]=[CH:9][N:10]=4)[N:7]=[C:2]([C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=4)[CH:3]=3)[CH:17]=[CH:16][CH:15]=2)[CH2:19]1

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 66827Phenylboronic AcidHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 86682717HCID 86682717, compound

Product 1

HCID 71525714HCID 71525714, compoundYield 40.2%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
100 °C

Procedure

A mixture of 6-chloro-N-(6-(3-methylpyrrolidin-1-yl)pyridin-2-yl)imidazo[1,2-b]pyridazin-8-amine (296 mg, 0.9 mmol), phenylboronic acid (165 mg, 1.35 mmol), Pd2(dba)3 (52 mg, 0.09 mmol), X-phos (172 mg, 0.36 mmol) and Na2CO3 (287 mg, 2.7 mmol) in dioxane (10 mL) and water (1 mL) was heated to 100° C. with stirring for 16 h under N2. The solution was removed in vacuo and the resulting mixture was purified by chromatography (silica gel, 200-300 mesh, petroleum ether:ethyl acetate=5:1) to give N-(6-(3-methylpyrrolidin-1-yl)pyridin-2-yl)-6-phenylimidazo[1,2-b]pyridazin-8-amine (134 mg, 40%) as a yellow solid. 1H NMR (300 MHz, CDCl3): δ 8.82 (s, 1H), 8.06-7.93 (m, 3H), 7.93-7.39 (m, 5H), 6.20 (d, 1H, J=7.8 Hz), 5.98 (d, 1H, J=8.1 Hz), 3.86-3.80 (m, 1H), 3.67-3.62 (m, 1H), 3.55-3.46 (m, 1H), 3.14 (t, 1H, J=9.3 Hz), 2.47-2.37 (m, 1H), 2.23-2.14 (m, 1H), 1.75-1.62 (m, 1H), 1.19 (d, 3H, J=6.6 Hz). LC-MS: [M+H]+, 371, tR=2.057 min, HPLC: 100% at 214 nm, 100% at 254 nm, tR=4.787 min.

Workup

  1. customThe solution was removed in vacuo
  2. customthe resulting mixture was purified by chromatography (silica gel, 200-300 mesh, petroleum ether:ethyl acetate=5:1)

Sources & evidence

ORD record
ord-717284075cd842d9957b85d46c933c33
Source dataset
uspto-grants-2015_10
Patent number
US09169259B2

Reaction notes

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