Hexane → 3-(3-Bromo-thieno[3,2-b]pyridin-2-yl)-8-(1-ethyl-propyl)-2,6-dimethyl-imidazo[1,2-b]pyridazine

HRID 226077Notes

Reaction equation

HRID 226077 reaction equation
[Br:1][C:2]1[C:6]2=[N:7][CH:8]=[CH:9][CH:10]=[C:5]2[S:4][CH:3]=1.[Li]CCCC.CCCCCC.[CH2:22]([CH:24]([C:27]1[C:28]2[N:29]([C:34](I)=[C:35]([CH3:37])[N:36]=2)[N:30]=[C:31]([CH3:33])[CH:32]=1)[CH2:25][CH3:26])[CH3:23]>C1COCC1.[Cl-].[Cl-].[Zn+2].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].C(Cl)Cl.O>[Br:1][C:2]1[C:6]2=[N:7][CH:8]=[CH:9][CH:10]=[C:5]2[S:4][C:3]=1[C:34]1[N:29]2[N:30]=[C:31]([CH3:33])[CH:32]=[C:27]([CH:24]([CH2:22][CH3:23])[CH2:25][CH3:26])[C:28]2=[N:36][C:35]=1[CH3:37]

Participants

10

Reactant 4

HCID 8058HexaneHCID 132204283-Bromothieno[3,2-b]pyridineHCID 577526818-(1-Ethyl-propyl)-3-iodo-2,6-dimethyl-imidazo[1,2-b]pyridazineHCID 178418339Butyllithium

Product 1

HCID 577526393-(3-Bromo-thieno[3,2-b]pyridin-2-yl)-8-(1-ethyl-propyl)-2,6-dimethyl-imidazo[1,2-b]pyridazineYield 22.1%

Reagents, catalysts & solvents 5

HCID 3007855ZincchlorideCatalystHCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

428 mg of 3-Bromo-thieno[3,2-b]pyridine (2.0 mmol) is dissolved in 2.0 ml of dry THF and cooled to −78° C. and 0.88 ml of n-BuLi 2.5M in hexane (2.2 mmol) is added slowly and the mixture is stirred at −78° C. for 15 min. 4.4 ml of ZnCl2 0.5M in THF (2.2 mmol) is added and stirred at room temperature for 20 min. 617 mg of 8-(1-ethyl-propyl)-3-iodo-2,6-dimethyl-imidazo[1,2-b]pyridazine (1.8 mmol) and 66 mg of PdCl2(dppf) (0.08 mmol) are added. The reaction vial is capped with a Teflon cap and heated at 80° C. overnight. Water and CH2Cl2 are added, and the separated CH2Cl2 layer is dried over Na2SO4 and evaporated. The crude product is applied onto a silica-gel chromatography column (Hexane:AcOEt=5:1) to produce the title compound 171 mg (22%), mass spectrum (m/e): 430; 1H-NMR (CDCl3): 8.84 (dd, 1H, J=4.5 Hz, 1.4 Hz), 8.20 (dd, 1H, J=8.4 Hz, 1.4 Hz), 7.37 (dd, 1H, J=8.4 Hz, 4.5 Hz), 6.75 (s, 1H), 3.34 (m, 1H), 2.56 (s, 3H), 2.51 (s, 3H), 1.85 (m, 4H), 0.89 (t, 6H, J=7.4 Hz) ppm.

Workup

  1. stirringstirred at room temperature for 20 min
  2. customThe reaction
  3. customcap
  4. temperatureheated at 80° C. overnight
  5. dry with materialthe separated CH2Cl2 layer is dried over Na2SO4
  6. customevaporated

Sources & evidence

ORD record
ord-87b8cfd742f743dd983b72722d74e862
Source dataset
uspto-grants-2009_07
Patent number
US07557103B2

Reaction notes

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