Hexane → 3-[5-(2,4-Dimethyl-thiazol-5-yl)-3-methyl-thiophen-2-yl]-8-(1-ethyl-propyl)-2,6-dimethyl-imidazo[1,2-b]pyridazine

HRID 1432598Notes

Reaction equation

HRID 1432598 reaction equation
[CH3:1][C:2]1[S:3][CH:4]=[C:5]([CH3:7])[N:6]=1.C([Li])(C)(C)C.CCCCCC.Br[C:20]1[S:24][C:23]([C:25]2[N:29]3[N:30]=[C:31]([CH3:39])[CH:32]=[C:33]([CH:34]([CH2:37][CH3:38])[CH2:35][CH3:36])[C:28]3=[N:27][C:26]=2[CH3:40])=[C:22]([CH3:41])[CH:21]=1>CCOC(C)=O.[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].C1COCC1>[CH3:1][C:2]1[S:3][C:4]([C:20]2[S:24][C:23]([C:25]3[N:29]4[N:30]=[C:31]([CH3:39])[CH:32]=[C:33]([CH:34]([CH2:37][CH3:38])[CH2:35][CH3:36])[C:28]4=[N:27][C:26]=3[CH3:40])=[C:22]([CH3:41])[CH:21]=2)=[C:5]([CH3:7])[N:6]=1

Participants

9

Reactant 4

HCID 8058HexaneHCID 109342,4-DimethylthiazoleHCID 579329433-(5-Bromo-3-methyl-thiophen-2-yl)-8-(1-ethyl-propyl)-2,6-dimethyl-imidazo[1,2-b]pyridazineHCID 178418306HCID 178418306, compound

Product 1

HCID 579329943-[5-(2,4-Dimethyl-thiazol-5-yl)-3-methyl-thiophen-2-yl]-8-(1-ethyl-propyl)-2,6-dimethyl-imidazo[1,2-b]pyridazineYield 49%

Reagents, catalysts & solvents 4

HCID 3007855ZincchlorideCatalystHCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-78 °C

Procedure

To a −78° C. mixture of 2,4-dimethylthiazole (0.23 g, 2.04 mmol) and THF (3 mL) is added 1.6 M t-Bu-Li in hexane (1.30 mL, 2.09 mmol). The mixture is stirred at −78° C. for 15 minutes. 0.5 M ZnCl2 in THF (4.3 mL, 2.14 mmol) is added and the solution warmed to ambient temperature. 3-(5-bromo-3-methyl-thiophen-2-yl)-8-(1-ethyl-propyl)-2,6-dimethyl-imidazo[1,2-b]pyridazine (0.40 g, 1.02 mmol) and PdCl2(dppf) (0.037 g, 0.051 mmol) is added and mixture is stirred at 65° C. overnight, diluted with EtOAc (20 mL), washed with 10% citric acid (15 mL), water (15 mL), brine (15 mL), dried over MgSO4, filtered and concentrated. The residue is purified by silica gel chromatography (0%-15% EtOAc/hexane gradient) furnish the title compound (0.21 g, 0.49 mmol, 49%). 1H NMR (CDCl3), δ 0.87 (t, J=7.5 Hz, 6H), 1.73-1.91 (m, 4H), 2.14 (s, 3H), 2.49 (s, 3H), 2.52 (s, 3H), 2.57 (s, 3H), 2.66 (s, 3H), 3.28-3.38 (m, 1H), 6.68 (s, 1H), 7.00 (s, 1H). LC/MS (m/z): calcd. for C23H28N4S2 (M+H)+: 425.3; found: 425.2.

Workup

  1. temperaturethe solution warmed to ambient temperature
  2. stirringmixture is stirred at 65° C. overnight
  3. washwashed with 10% citric acid (15 mL), water (15 mL), brine (15 mL)
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue is purified by silica gel chromatography (0%-15% EtOAc/hexane gradient)

Sources & evidence

ORD record
ord-4c5e27eaefd34671aa9ceaac4f1efac9
Source dataset
uspto-grants-2009_11
Patent number
US07612067B2

Reaction notes

Loading…