Sodium Carbonate → HCID 71526536, compound

HRID 1755414Notes

Reaction equation

HRID 1755414 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.[N:24]1[CH:29]=[CH:28][C:27](B(O)O)=[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.[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:27]3[CH:28]=[CH:29][N:24]=[CH:25][CH:26]=3)[CH:3]=2)[CH:17]=[CH:16][CH:15]=1

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 2734379(Pyridin-4-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 71526536HCID 71526536, compoundYield 44.9%

Reagents, catalysts & solvents 2

HCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladiumCatalystHCID 218864351,4-Dioxane--water (1/1)Solvent

Conditions

Temperature
95 °C

Procedure

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), pyridin-4-ylboronic acid (0.022 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 N-(6-(2-methylpyrrolidin-1-yl)pyridin-2-yl)-6-(pyridin-4-yl)imidazo[1,2-b]pyridazin-8-amine (0.025 g, 44%) as a yellow solid. 1H NMR (300 MHz, CDCl3): δ 8.75-8.70 (m, 3H), 8.15 (brs, 1H), 7.93 (s, 1H), 7.86 (d, 1H, J=5.7 Hz), 7.62 (s, 1H), 7.41 (t, 1H, J=7.9 Hz), 6.22 (d, 1H, J=7.5 Hz), 6.05 (d, 1H, J=8.4 Hz), 4.26-4.22 (m, 1H), 3.68-3.63 (m, 1H), 3.49-3.46 (m, 1H), 2.16-2.04 (m, 3H), 1.77 (brs, 1H), 1.24 (t, 3H, J=6.3 Hz). LC/MS: 372 [M+H]+, 370 [M−H]−, tR=1.68 min. HPLC: 100% at 214 nm, 100% at 254 nm, tR=4.57 min.

Workup

  1. customThe solvent was removed in vacuo
  2. customthe residue purified by chromatography (silica gel, petroleum ether/ethyl acetate 3:1)

Sources & evidence

ORD record
ord-855aa4fb14ef41f2a05675814cbedfb4
Source dataset
uspto-grants-2015_10
Patent number
US09169259B2

Reaction notes

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