Dichloromethane → 5-(6-(2-(2,5-Dimethylphenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)-2-fluorobenzonitrile

HRID 1890678Notes

Reaction equation

HRID 1890678 reaction equation
C(=O)([O-])[O-].[Na+].[Na+].[C:7]([C:9]1[CH:10]=[C:11](B(O)O)[CH:12]=[CH:13][C:14]=1[F:15])#[N:8].ClCCl.Br[C:23]1[N:27]2[N:28]=[C:29]([N:32]3[CH2:36][CH2:35][CH2:34][CH:33]3[C:37]3[CH:42]=[C:41]([CH3:43])[CH:40]=[CH:39][C:38]=3[CH3:44])[CH:30]=[CH:31][C:26]2=[N:25][CH:24]=1>O1CCOCC1.O>[CH3:44][C:38]1[CH:39]=[CH:40][C:41]([CH3:43])=[CH:42][C:37]=1[CH:33]1[CH2:34][CH2:35][CH2:36][N:32]1[C:29]1[CH:30]=[CH:31][C:26]2[N:27]([C:23]([C:11]3[CH:12]=[CH:13][C:14]([F:15])=[C:9]([CH:10]=3)[C:7]#[N:8])=[CH:24][N:25]=2)[N:28]=1

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 27579643-Cyano-4-fluorophenylboronic acidHCID 583354743-Bromo-6-(2-(2,5-dimethylphenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazine

Product 1

HCID 445204395-(6-(2-(2,5-Dimethylphenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)-2-fluorobenzonitrile

Reagents, catalysts & solvents 1

HCID 218864351,4-Dioxane--water (1/1)Solvent

Procedure

In step 4-2, sodium carbonate (30 mg, 0.30 mmol), 3-cyano-4-fluoro phenylboronic acid (30 mg, 0.24 mmol) and Pd(DPPF)-dichloride catalyst (1,1′ bis(diphenylsphosphino-ferrocene)-dichloropalladium (II) adduct with dichloromethane) (10 mg, 0.012 mmol) was added into in a microwave vessel containing a solution of 3-bromo-6-(2-(2,5-dimethylphenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazine (50 mg, 0.13 mmol) and 2.5 mL of 1,4-dioxane/water (3:1). The reaction mixture was subjected to the following microwave conditions using a laboratory microwave instrument (conditions: 150° C., 200 W max threshold, 20 atm. Max pressure, 20 minute reaction time). The resulting solution was purified using preparatory LC/MS (reverse phase C-18 chromatography) to yield 5-(6-(2-(2,5-dimethylphenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)-2-fluorobenzonitrile (4-2). 1H NMR (400 MHz, D3 acetonitrile) δ ppm 8.50-8.10 (m, 2H), 7.80 (br s, 1H), 7.50 (app d, J=8.5 Hz, 1H), 7.20 (app t, J=6.5 Hz, 1H), 7.06 (d, J=6.5 Hz, 1H), 6.93 (d, J=6.6 Hz, 1H), 6.81 (br s, 1H), 6.60 (br s, 1H), 5.22 (app dd, J=6.2, 2.1 Hz, 1H), 4.05-4.00 (m, 1H), 3.76 (app q, J=6.4 Hz, 1H), 3.36 (app d, J=2.2 Hz, 1H), 2.58-2.43 (m, 1H), 2.24 (br s, 6H), 2.19-2.08 (m, 2H). LCMS observed m/z 412.2.

Workup

  1. customa laboratory microwave instrument (conditions: 150° C., 200 W max threshold, 20 atm. Max pressure, 20 minute reaction time)
  2. customThe resulting solution was purified

Sources & evidence

ORD record
ord-66e104648fd54965a14fcf39d53e6c97
Source dataset
uspto-grants-2013_08
Patent number
US08507488B2

Reaction notes

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