3-(5-Bromo-3-chloro-thiophen-2-yl)-8-(1-ethyl-propyl)-2,6-dimethyl-imidazo[1,2-b]pyridazine → 3-(3-Chloro-5-pyridin-2-yl-thiophen-2-yl)-8-(1-ethyl-propyl)-2,6-dimethyl-imidazo[1,2-b]pyridazine

HRID 1432640Notes

Reaction equation

HRID 1432640 reaction equation
Br[C:2]1[S:6][C:5]([C:7]2[N:11]3[N:12]=[C:13]([CH3:21])[CH:14]=[C:15]([CH:16]([CH2:19][CH3:20])[CH2:17][CH3:18])[C:10]3=[N:9][C:8]=2[CH3:22])=[C:4]([Cl:23])[CH:3]=1.[Br-].[N:25]1[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=1[Zn+]>CCOC(C)=O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[Cl:23][C:4]1[CH:3]=[C:2]([C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][N:25]=2)[S:6][C:5]=1[C:7]1[N:11]2[N:12]=[C:13]([CH3:21])[CH:14]=[C:15]([CH:16]([CH2:19][CH3:20])[CH2:17][CH3:18])[C:10]2=[N:9][C:8]=1[CH3:22]

Participants

5

Reactant 2

HCID 579329223-(5-Bromo-3-chloro-thiophen-2-yl)-8-(1-ethyl-propyl)-2,6-dimethyl-imidazo[1,2-b]pyridazineHCID 178418723HCID 178418723, compound

Product 1

HCID 579330863-(3-Chloro-5-pyridin-2-yl-thiophen-2-yl)-8-(1-ethyl-propyl)-2,6-dimethyl-imidazo[1,2-b]pyridazineYield 60%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
65 °C

Procedure

To a flask containing 3-(5-bromo-3-chloro-thiophen-2-yl)-8-(1-ethyl-propyl)-2,6-dimethyl-imidazo[1,2-b]pyridazine (0.25 g, 0.61 mmol) and PdCl2(dppf) (0.022 g, 0.030 mmol) is added a 0.5 M solution of 2-pyridylzinc bromide (2.40 mL, 1.21 mmol) and the solution heated at 65° C. overnight, diluted with EtOAc (30 mL), washed with sat. NH4Cl (2×30 mL), dried over MgSO4, filtered and concentrated. The residue is purified by ISCO column chromatography (20%-40% EtOAc/hexane gradient) followed by recrystallization from CH3CN furnish the title compound (0.15 g, 0.36 mmol, 60%). 1H NMR (CDCl3) δ 0.88 (d, J=7.5 Hz, 6H), 1.73-1.93 (m, 4H), 2.52 (s, 3H), 2.53 (s, 3H), 3.29-3.38 (m, 1H), 6.70 (s, 1H), 7.17-7.23 (m, 1H), 7.56 (s, 1H), 7.66 (d, J=7.9 Hz, 1H), 7.70-7.76 (m, 1H), 8.59 (d, J=4.7 Hz, 1H). LC/MS (m/z): calcd. for C22H23ClN4S (M+H)+: 412.0; found: 412.4.

Workup

  1. washwashed with sat. NH4Cl (2×30 mL)
  2. dry with materialdried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue is purified by ISCO column chromatography (20%-40% EtOAc/hexane gradient)
  6. customfollowed by recrystallization from CH3CN

Sources & evidence

ORD record
ord-bf093bf66766449bbab594e47b095a06
Source dataset
uspto-grants-2009_11
Patent number
US07612067B2

Reaction notes

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