Sodium Carbonate → HCID 71526264, compound

HRID 1755381Notes

Reaction equation

HRID 1755381 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.[CH3:24][O:25][C:26]1[CH:27]=[C:28](B(O)O)[CH:29]=[CH:30][C:31]=1[O:32][CH3:33].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]>[CH3:24][O:25][C:26]1[CH:27]=[C:28]([C:2]2[CH:3]=[C:4]([NH:11][C:12]3[CH:17]=[CH:16][CH:15]=[C:14]([N:18]4[CH2:22][CH2:21][CH2:20][CH:19]4[CH3:23])[N:13]=3)[C:5]3[N:6]([CH:8]=[CH:9][N:10]=3)[N:7]=2)[CH:29]=[CH:30][C:31]=1[O:32][CH3:33]

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 27347023,4-Dimethoxyphenylboronic 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 71526264HCID 71526264, compoundYield 14%

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 (100 mg, 0.3 mmol), 3,4-dimethoxyphenylboronic acid (82 mg, 0.45 mmol), Pd2(dba)3 (0.018 g, 0.03 mmol), X-phos (0.029 g, 0.06 mmol) and Na2CO3 (0.096 g, 0.9 mmol) in dioxane (3 mL) and water (3 mL) was heated to 100° C. for 15 h in a sealed tube under N2 atmosphere then concentrated in vacuo. The residue was purified by prep-HPLC (Gemini 5u C18 150×21.2 mm; inject volume: 3 mL/inj, flow rate: 20 mL/min; wavelength: 214 nm and 254 nm; gradient conditions: 20% acetonitrile/80% water (0.1% TFA, v/v) initially, proceeding to 50% acetonitrile/50% water (0.1% TFA, v/v) in a linear fashion over 9 min) to afford 6-(3,4-dimethoxyphenyl)-N-(6-(2-methylpyrrolidin-1-yl)pyridin-2-yl)imidazo[1,2-b]pyridazin-8-amine (18 mg, 14%) as a yellow solid. 1H NMR (300 MHz, DMSO): δ 10.19 (s, 1H), 8.93 (s, 1H), 8.40 (s, 1H), 8.08 (s, 1H), 7.50-7.48 (m, 1H), 7.11 (d, 1H, J=8.4 Hz), 6.66 (d, 1H, J=7.2 Hz), 6.12 (d, 1H, J=7.8 Hz), 4.22 (brs, 1H), 3.85 (s, 6H), 3.56-3.37 (m, 3H), 2.07-1.97 (m, 2H), 1.74-1.70 (m, 1H), 1.11 (d, 3H, J=6.3 Hz). LC-MS: [M+H]+, 431, tR=1.769 min, HPLC: 98.38% at 214 nm, 99.04% at 254 nm, tR=7.213 min.

Workup

  1. concentrationthen concentrated in vacuo
  2. customThe residue was purified by prep-HPLC (Gemini 5u C18 150×21.2 mm

Sources & evidence

ORD record
ord-9fb49147ed8849648d4410ab36509254
Source dataset
uspto-grants-2015_10
Patent number
US09169259B2

Reaction notes

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