3-(4-Bromo-3-methyl-thiophen-2-yl)-8-(1-ethyl-propyl)-2,6-dimethyl-imidazo[1,2-b]pyridazine → HCID 57932926, compound

HRID 1432616Notes

Reaction equation

HRID 1432616 reaction equation
Br[C:2]1[C:3]([CH3:23])=[C:4]([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])[S:5][CH:6]=1.[Br-].[S:25]1[CH:29]=[CH:28][N: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]>[CH2:17]([CH:16]([C:15]1[C:10]2[N:11]([C:7]([C:4]3[S:5][CH:6]=[C:2]([C:26]4[S:25][CH:29]=[CH:28][N:27]=4)[C:3]=3[CH3:23])=[C:8]([CH3:22])[N:9]=2)[N:12]=[C:13]([CH3:21])[CH:14]=1)[CH2:19][CH3:20])[CH3:18]

Participants

5

Reactant 2

HCID 579329703-(4-Bromo-3-methyl-thiophen-2-yl)-8-(1-ethyl-propyl)-2,6-dimethyl-imidazo[1,2-b]pyridazineHCID 178419763HCID 178419763, compound

Product 1

HCID 57932926HCID 57932926, compoundYield 76%

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-(4-bromo-3-methyl-thiophen-2-yl)-8-(1-ethyl-propyl)-2,6-dimethyl-imidazo[1,2-b]pyridazine (0.25 g, 0.64 mmol) and PdCl2(dppf) (0.023 g, 0.032 mmol) is added a 0.5 M solution of 2-thiazolylzinc bromide (3.82 mL, 1.91 mmol). The solution is heated at 65° C. overnight, diluted with EtOAc (30 mL), washed with sat. NH4Cl (25 mL), dried over MgSO4, filtered and concentrated. The residue is purified by ISCO (15%-20% EtOAc gradient) furnish the title compound (0.19 g, 0.48 mmol, 76%). 1H NMR (CDCl3) δ 0.88 (t, J=7.5 Hz, 6H), 1.75-1.92 (m, 4H), 2.36 (s, 3H), 2.47 (s, 3H), 2.50 (, 3H), 3.29-3.39 (m, 1H), 6.69 (s, 1H), 7.33 (d, J=3.3 Hz, 1H), 7.89 (d, J=3.3 Hz, 1H), 7.99 (s, 1H). LC/MS (m/z): calcd. for C21H24N4S2 (M+H)+: 397.2; found: 397.3.

Workup

  1. washwashed with sat. NH4Cl (25 mL)
  2. dry with materialdried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue is purified by ISCO (15%-20% EtOAc gradient)

Sources & evidence

ORD record
ord-28077f2501f7403faf6204f8e50b543c
Source dataset
uspto-grants-2009_11
Patent number
US07612067B2

Reaction notes

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