Ethyl Acetate → HCID 57932941, compound

HRID 1432574Notes

Reaction equation

HRID 1432574 reaction equation
Br[C:2]1[S:6][C:5]([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])=[C:4]([CH3:23])[CH:3]=1.C[CH2:25][O:26][C:27](C)=[O:28]>CO.CS(C)=O.CCN(CC)CC.CC([O-])=O.CC([O-])=O.[Pd+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.[Fe+2]>[CH3:25][O:26][C:27]([C:2]1[S:6][C:5]([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])=[C:4]([CH3:23])[CH:3]=1)=[O:28]

Participants

8

Reactant 2

HCID 8857Ethyl AcetateHCID 579329433-(5-Bromo-3-methyl-thiophen-2-yl)-8-(1-ethyl-propyl)-2,6-dimethyl-imidazo[1,2-b]pyridazine

Product 1

HCID 57932941HCID 57932941, compoundYield 80%

Reagents, catalysts & solvents 5

HCID 167845palladium(II) acetateCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 679Dimethyl SulfoxideSolventHCID 887MethanolSolventHCID 8471TriethylamineSolvent

Procedure

A solution of 3-(5-bromo-3-methyl-thiophen-2-yl)-8-(1-ethyl-propyl)-2,6-dimethyl-imidazo[1,2-b]pyridazine (1.00 g, 2.66 mmol) in CH3OH (12 mL), DMSO (18 mL), Et3N (2.0 mL) with Pd(OAc)2 (0.12 g, 0.538 mmol), dppf (0.937 g, 1.69 mmol) is reacted at CO atmosphere (100 psi) at 80° C. for 24 h. The reaction mixture is diluted with EtOAc (200 mL), washed with 0.1 M HCl (2×50 mL), brine (50 mL); dried with Na2SO4; filtered through silica gel and eluted with excess EtOAc. Purification of the crude material by chromatography gives the title compound (0.79 g, 2.12 mmol, 80%). 1H NMR (CDCl3): δ 0.89 (t, J=7.7 Hz, 6H), 1.75-1.93 (m, 4H), 2.15 (s, 3H), 2.50 (s, 3H), 2.53 (s, 3H), 3.32-3.42 (m, 1H), 3.91 (s, 3H), 6.72 (s, 1H), 7.73 (s, 1H). ES-MS (m/z): calcd for C20H25N3O2S (M+H)+: 372.5; found: 372.2.

Workup

  1. washwashed with 0.1 M HCl (2×50 mL), brine (50 mL)
  2. dry with materialdried with Na2SO4
  3. filtrationfiltered through silica gel
  4. washeluted with excess EtOAc
  5. customPurification of the crude material by chromatography

Sources & evidence

ORD record
ord-2a5b5c2470704d5c89c42827c9649fa6
Source dataset
uspto-grants-2009_11
Patent number
US07612067B2

Reaction notes

Loading…