Cesium carbonate → 2-Fluoro-4-(8-((4-methoxybenzyl)(phenyl)amino)imidazo[1,2-b]pyridazin-6-yl)benzonitrile

HRID 2239884Notes

Reaction equation

HRID 2239884 reaction equation
Cl[C:2]1[CH:3]=[C:4]([N:11]([CH2:18][C:19]2[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][CH:20]=2)[C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[C:5]2[N:6]([CH:8]=[CH:9][N:10]=2)[N:7]=1.[C:27]([C:29]1[CH:34]=[CH:33][C:32](B(O)O)=[CH:31][C:30]=1[F:38])#[N:28].C(=O)([O-])[O-].[Cs+].[Cs+]>[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CN(C=O)C>[F:38][C:30]1[CH:31]=[C:32]([C:2]2[CH:3]=[C:4]([N:11]([CH2:18][C:19]3[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][CH:20]=3)[C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)[C:5]3[N:6]([CH:8]=[CH:9][N:10]=3)[N:7]=2)[CH:33]=[CH:34][C:29]=1[C:27]#[N:28]

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 2783130(4-Cyano-3-fluorophenyl)boronic acidHCID 596245586-chloro-N-(4-methoxybenzyl)-N-phenylimidazo[1,2-b]pyridazin-8-amine

Product 1

HCID 684836572-Fluoro-4-(8-((4-methoxybenzyl)(phenyl)amino)imidazo[1,2-b]pyridazin-6-yl)benzonitrileYield 24.4%

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

To a vial was added 6-chloro-N-(4-methoxybenzyl)-N-phenyl imidazo[1,2-b]pyridazin-8-amine (100 mg, 0.274 mmol) from Example XXXVI(1) step (1a), 4-cyano-3-fluorophenylboronic acid (49.7 mg, 0.302 mmol), tetrakis(triphenylphosphine) palladium (17.4 mg, 0.015 mmol) and cesium carbonate (295 mg, 0.905 mmol in water (0.2 mL)) and DMF (2 mL). The solution was heated to 100° C. for 10 hours. The crude product mixture was filtered through celite, concentrated in vacuo and purified by preparative HPLC to give 2-fluoro-4-(8-((4-methoxybenzyl)(phenyl)amino)imidazo[1,2-b]pyridazin-6-yl)benzonitrile (30 mg, 24%). LC/MS, m/e 463 (M+1). HPLC Rt, 3.80 min. Waters Sunfire C18 column (4.6×50 mm). 0%-100% B. Solvent B: (90% MeOH, 10% H2O, 0.1% TFA). Solvent A: (10% MeOH, 90% H2O, 0.1% TFA). Gradient, start % B=0, final % B=100, gradient time 4 min hold at 100% B 1 min, flow rate 4 mL/min.

Workup

  1. filtrationThe crude product mixture was filtered through celite
  2. concentrationconcentrated in vacuo
  3. custompurified by preparative HPLC

Sources & evidence

ORD record
ord-2bee74af21a6465fa23e86fe049171ab
Source dataset
uspto-grants-2010_05
Patent number
US07723336B2

Reaction notes

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