Lithium diisopropylamide → 1-{3-[3-Chloro-5-(2-methyl-2H-[1,2,4]triazol-3-yl)-thiophen-2-yl]-2,6-dimethyl-imidazo[1,2-b]pyridazin-8-yl}-butan-1-one

HRID 1432681Notes

Reaction equation

HRID 1432681 reaction equation
[Cl:1][C:2]1[CH:6]=[C:5]([C:7]2[N:8]([CH3:12])[N:9]=[CH:10][N:11]=2)[S:4][C:3]=1[C:13]1[N:17]2[N:18]=[C:19]([CH3:22])[CH:20]=[CH:21][C:16]2=[N:15][C:14]=1[CH3:23].[Li+].CC([N-]C(C)C)C.CCCCCCC.[CH2:39]1[CH2:43][O:42][CH2:41][CH2:40]1.C(C1C=CC=CC=1)C>C1COCC1.ClCCl>[Cl:1][C:2]1[CH:6]=[C:5]([C:7]2[N:8]([CH3:12])[N:9]=[CH:10][N:11]=2)[S:4][C:3]=1[C:13]1[N:17]2[N:18]=[C:19]([CH3:22])[CH:20]=[C:21]([C:41](=[O:42])[CH2:40][CH2:39][CH3:43])[C:16]2=[N:15][C:14]=1[CH3:23]

Participants

6

Reactant 3

HCID 2724682Lithium diisopropylamideHCID 22742125Tetrahydrofuran heptane ethylbenzolHCID 57932899HCID 57932899, compound

Product 1

HCID 579330721-{3-[3-Chloro-5-(2-methyl-2H-[1,2,4]triazol-3-yl)-thiophen-2-yl]-2,6-dimethyl-imidazo[1,2-b]pyridazin-8-yl}-butan-1-oneYield 46.6%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of 3-[3-chloro-5-(2-methyl-2H-[1,2,4]triazol-3-yl)-thiophen-2-yl]-2,6-dimethyl-imidazo[1,2-b]pyridazine (0.20 g, 0.58 mmol), N-methoxy-N-methyl-butylamide (Wolberg, M. et. al. Chem. Europ. J. 2001, 7, 4562) (0.084 g, 0.64 mmol) in THF (3 mL) is cooled to a −78° C., and a 2.0 M solution of LDA in heptane/THF/ethyl benzene (0.58 mL, 1.16 mmol) is added. The solution is warmed to ambient temperature, diluted with dichloromethane (20 mL), and washed with a sat. NH4Cl solution (15 mL). The organic layer is dried over MgSO4, filtered and concentrated. The residue is purified by ISCO flash chromatography (20%-100% EtOAc gradient) to furnish the title compound (0.11 g, 0.27 mmol, 46%). 1H-NMR (CDCl3), δ 1.04 (t, J=7.0 Hz, 3H), 1.76-1.86 (m, 2H), 2.56 (s, 3H), 2.59 (s, 3H), 3.51 (t, J=7.1 Hz, 2H), 4.15 (s, 3H), 7.36 (s, 1H), 7.49 (s, 1H), 7.90 (s, 1H) ppm. LC/MS (m/z): calcd. for C19H19ClN6OS (M+H)+: 415.1; found: 415.3.

Workup

  1. washwashed with a sat. NH4Cl solution (15 mL)
  2. dry with materialThe organic layer is dried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue is purified by ISCO flash chromatography (20%-100% EtOAc gradient)

Sources & evidence

ORD record
ord-27f7f90458074da1b0916b836bcda7df
Source dataset
uspto-grants-2009_11
Patent number
US07612067B2

Reaction notes

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