Tetrahydrofuran → 1-{2,6-Dimethyl-3-[3-methyl-5-(6-methyl-pyridin-2-yl)-thiophen-2-yl]-imidazo[1,2-b]pyridazin-8-yl}-propan-1-one

HRID 1432614Notes

Reaction equation

HRID 1432614 reaction equation
[CH3:1][C:2]1[N:3]=[C:4]2[CH:9]=[CH:8][C:7]([CH3:10])=[N:6][N:5]2[C:11]=1[C:12]1[S:13][C:14]([C:18]2[CH:23]=[CH:22][CH:21]=[C:20]([CH3:24])[N:19]=2)=[CH:15][C:16]=1[CH3:17].[CH2:25]1C[O:28][CH2:27][CH2:26]1.[Li+].CC([N-]C(C)C)C.CON(C)C(=O)CC>CCOC(C)=O>[CH3:1][C:2]1[N:3]=[C:4]2[C:9]([C:27](=[O:28])[CH2:26][CH3:25])=[CH:8][C:7]([CH3:10])=[N:6][N:5]2[C:11]=1[C:12]1[S:13][C:14]([C:18]2[CH:23]=[CH:22][CH:21]=[C:20]([CH3:24])[N:19]=2)=[CH:15][C:16]=1[CH3:17]

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 2724682Lithium diisopropylamideHCID 11344007N-Methoxy-N-methylpropionamideHCID 688416742,6-Dimethyl-3-[3-methyl-5-(6-methyl-pyridin-2-yl)-thiophen-2-yl]-imidazo[1,2-b]pyridazine

Product 1

HCID 688400841-{2,6-Dimethyl-3-[3-methyl-5-(6-methyl-pyridin-2-yl)-thiophen-2-yl]-imidazo[1,2-b]pyridazin-8-yl}-propan-1-oneYield 25%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a −78° C. solution of 2,6-dimethyl-3-[3-methyl-5-(6-methyl-pyridin-2-yl)-thiophen-2-yl]-imidazo[1,2-b]pyridazine (0.34 g, 1.02 mmol) and THF (9 mL) is added 2.0 M LDA (0.61 mL, 1.22 mmol). After 3 minutes, N-methoxy-N-methyl-propionamide (Wolberg et. el. Chem. Eur. J., 2001, 7, 4562) (1.17 g, 1.42 mmol) is added and the solution stirred for 20 minutes, warmed to ambient temperature and stirred for 30 minutes. The solution is diluted with EtOAc (50 mL) washed with sat. NH4Cl (30 mL), dried over MgSO4, filtered and concentrated. The residue is purified by ISCO column chromatography (20%-30% EtOAc/hexane gradient) furnish the title compound (0.10 g, 0.26 mmol, 25%). 1H NMR (CDCl3), δ 1.28 (t, J=7.0 Hz, 3H), 2.13 (s, 3H), 2.54 (s, 3H), 2.58 (s, 6H), 3.59 (q, J=7.0 Hz, 2H), 7.03 (d, J=7.5 Hz, 1H), 7.33 (s, 1H), 7.47 (d, J=7.9 Hz, 1H), 7.55 (bs, 1H), 7.58 (dd, J=7.9, 7.5 Hz, 1H). LC/MS (m/z): calcd. for C22H22N4OS (M+H)+: 391.2; found: 391.2.

Workup

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

Sources & evidence

ORD record
ord-ac30183a34414b48b3617e5e0b4f80a8
Source dataset
uspto-grants-2009_11
Patent number
US07612067B2

Reaction notes

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