Tetrahydrofuran → HCID 57932967, compound

HRID 1432609Notes

Reaction equation

HRID 1432609 reaction equation
Br[C:2]1[N:7]=[C:6]([C:8]2[S:12][C:11]([C:13]3[N:17]4[N:18]=[C:19]([CH3:27])[CH:20]=[C:21]([CH:22]([CH2:25][CH3:26])[CH2:23][CH3:24])[C:16]4=[N:15][C:14]=3[CH3:28])=[C:10]([CH3:29])[CH:9]=2)[CH:5]=[CH:4][CH:3]=1.C1C[O:33][CH2:32][CH2:31]1.C([Li])CCC.CON(C)C(=O)C>CCOC(C)=O>[CH2:23]([CH:22]([C:21]1[C:16]2[N:17]([C:13]([C:11]3[S:12][C:8]([C:6]4[N:7]=[C:2]([C:32](=[O:33])[CH3:31])[CH:3]=[CH:4][CH:5]=4)=[CH:9][C:10]=3[CH3:29])=[C:14]([CH3:28])[N:15]=2)[N:18]=[C:19]([CH3:27])[CH:20]=1)[CH2:25][CH3:26])[CH3:24]

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 537505N-Methoxy-N-methylacetamideHCID 86620091HCID 86620091, compoundHCID 178418339Butyllithium

Product 1

HCID 57932967HCID 57932967, compoundYield 13%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a −78° C. solution of 3-[5-(6-bromo-pyridin-2-yl)-3-methyl-thiophen-2-yl]-8-(1-ethyl-propyl)-2,6-dimethyl-imidazo[1,2-b]pyridazine) (0.26 g, 0.55 mmol), and THF (5 mL), is added 1.34 M n-Bu-Li (0.43 mL, 0.58 mmol). After 30 minutes N-methoxy-N-methyl-acetamide (0.065 mL, 0.61 mmol) is added and the solution warmed to ambient temperature. The solution is diluted with EtOAc (30 mL), washed with sat. NH4Cl (25 mL), dried over MgSO4, filtered and concentrated. The residue is purified by ISCO column chromatography (15-20% EtOAc/hexane gradient) furnish the title compound (0.030 g, 0.069 mmol, 13%). 1H NMR (CDCl3), δ 0.89 (t, J=7.5 Hz, 6H), 1.75-1.93 (m, 4H), 2.19 (s, 3H), 2.52 (s, 3H), 2.53 (s, 3H), 2.77 (s, 3H), 3.30-3.40 (m, 1H), 6.69 (s, 1H), 7.59 (s, 1H), 7.77-7.85 (m, 2H), 7.87 (dd, J=6.8, 2.2 Hz, 1H). LC/MS (m/z): calcd. for C25H28N4OS (M+H)+: 433.3; found: 433.2.

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 column chromatography (15-20% EtOAc/hexane gradient)

Sources & evidence

ORD record
ord-9d228279a7314264ae96be9a7fad2f93
Source dataset
uspto-grants-2009_11
Patent number
US07612067B2

Reaction notes

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