Dichloromethane → HCID 44520266, compound

HRID 1890676Notes

Reaction equation

HRID 1890676 reaction equation
C(=O)([O-])[O-].[Na+].[Na+].[C:7]([C:9]1[CH:10]=[C:11](B(O)O)[CH:12]=[CH:13][CH:14]=1)#[N:8].ClCCl.Br[C:22]1[N:26]2[N:27]=[C:28]([N:31]3[CH2:35][CH2:34][C@H:33]([OH:36])[CH:32]3[C:37]3[CH:42]=[CH:41][CH:40]=[C:39]([F:43])[CH:38]=3)[CH:29]=[CH:30][C:25]2=[N:24][CH:23]=1>O1CCOCC1.O>[F:43][C:39]1[CH:38]=[C:37]([CH:32]2[C@@H:33]([OH:36])[CH2:34][CH2:35][N:31]2[C:28]2[CH:29]=[CH:30][C:25]3[N:26]([C:22]([C:13]4[CH:14]=[C:9]([CH:10]=[CH:11][CH:12]=4)[C:7]#[N:8])=[CH:23][N:24]=3)[N:27]=2)[CH:42]=[CH:41][CH:40]=1

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 27343253-Cyanophenylboronic acidHCID 58335815HCID 58335815, compound

Product 1

HCID 44520266HCID 44520266, compound

Reagents, catalysts & solvents 1

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

Procedure

In step 3-5, in a microwave vessel sodium carbonate (105 mg, 1.0 mmol), 3-cyano phenylboronic acid (200 mg, 1.36 mmol) and Pd(DPPF)-dichloride catalyst (1,1′ bis(diphenylsphosphino-ferrocene)-dichloropalladium (II) adduct with dichloromethane) (100 mg, 0.12 mmol) were added to a solution (3S)-1-(3-bromoimidazo[1,2-b]pyridazin-6-yl)-2-(3-fluorophenyl)pyrrolidin-3-ol (1.40 g, 0.36 mmol) and 4 mL of 1,4-dioxane/water (3:1). This solution was then 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 reaction mixture was purified directly with reverse phase C-18 HPLC (water/acetonitrile 90:10 to 10:90 gradient) to yield 3-(6-((3S)-2-(3-fluorophenyl)-3-hydroxypyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)benzonitrile (3-5) as a mixture of diastereomers. 1H NMR (400 MHz, D6 acetone) δ ppm 8.85 (br s, 1H), 8.40-8.03 (m, 3H), 7.90-7.22 (m, 5H), 7.10 (app d, J=5.5 Hz, 1H), 6.98 (app t, J=4.5 Hz, 1H), 5.25 (app d, J=4.5 Hz, 1H), 4.80 (app q, J=7.5 Hz, 1H), 4.30 (br s, 1H), 3.82-3.75 (m, 1H), 3.3-3.55 (m, 1H), 2.42-2.34 (m, 1H), 2.25-2.12 (m, 1H). LCMS observed m/z 400.2.

Workup

  1. customa laboratory microwave instrument (conditions: 150° C., 200 W max threshold, 20 atm. max pressure, 20 minute reaction time)
  2. customThe reaction mixture was purified directly with reverse phase C-18 HPLC (water/acetonitrile 90:10 to 10:90 gradient)

Sources & evidence

ORD record
ord-dbdb823768df41189650d5c38a748017
Source dataset
uspto-grants-2013_08
Patent number
US08507488B2

Reaction notes

Loading…