Ethyl Acetate → tert-Butyl 3-(8-morpholino-2-(quinolin-2-ylethynyl)imidazo[1,2-b]pyridazin-3-yl)benzoate

HRID 718587Notes

Reaction equation

HRID 718587 reaction equation
Br[C:2]1[N:6]2[N:7]=[CH:8][CH:9]=[C:10]([N:11]3[CH2:16][CH2:15][O:14][CH2:13][CH2:12]3)[C:5]2=[N:4][C:3]=1[C:17]#[C:18][C:19]1[CH:28]=[CH:27][C:26]2[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=2)[N:20]=1.[C:29]([O:33][C:34]([C:36]1[CH:37]=[C:38](B(O)O)[CH:39]=[CH:40][CH:41]=1)=[O:35])([CH3:32])([CH3:31])[CH3:30].C(=O)([O-])[O-].[Cs+].[Cs+].CCOC(C)=O>O1CCOCC1.O>[O:14]1[CH2:15][CH2:16][N:11]([C:10]2[C:5]3[N:6]([C:2]([C:40]4[CH:41]=[C:36]([CH:37]=[CH:38][CH:39]=4)[C:34]([O:33][C:29]([CH3:31])([CH3:32])[CH3:30])=[O:35])=[C:3]([C:17]#[C:18][C:19]4[CH:28]=[CH:27][C:26]5[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=5)[N:20]=4)[N:4]=3)[N:7]=[CH:8][CH:9]=2)[CH2:12][CH2:13]1

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 10796Cesium carbonateHCID 2773299(3-((Tert-butoxy)carbonyl)phenyl)boronic acidHCID 1177283744-(3-Bromo-2-(quinolin-2-ylethynyl)imidazo[1,2-b]pyridazin-8-yl)morpholine

Product 1

HCID 117732464tert-Butyl 3-(8-morpholino-2-(quinolin-2-ylethynyl)imidazo[1,2-b]pyridazin-3-yl)benzoate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

To a stirred solution of compound 18b (51 mg, 0.12 mmol), (3-(tert-butoxycarbonyl)phenyl)boronic acid (39 mg, 0.18 mmol), and cesium carbonate (0.12 g, 0.36 mmol) in degassed 1,4-dioxane (4 mL) and water (0.5 mL) under Argon was added dichloro(diphenylphosphinoferrocene)palladium (II) (4.3 mg, 0.0059 mmol). The resulting mixture was heated at 80° C. for 2 h, allowed to cool to rt, and treated with EtOAc (10 mL). The organic layer was washed with water (10 mL) and brine (10 mL), and dried over Na2SO4. The mixture was filtered, and the filtrate was concentrated. The resulting residue was purified by flash column chromatography on silica gel (20-100% EtOAc/heptane) to give compound 18c as a brown oil. Mass Spectrum (LCMS, ESI pos.): Calcd. for C32H29N5O3: 532.2 (M+H). found: 532.5.

Workup

  1. temperatureto cool to rt
  2. washThe organic layer was washed with water (10 mL) and brine (10 mL)
  3. dry with materialdried over Na2SO4
  4. filtrationThe mixture was filtered
  5. concentrationthe filtrate was concentrated
  6. customThe resulting residue was purified by flash column chromatography on silica gel (20-100% EtOAc/heptane)

Sources & evidence

ORD record
ord-b1e16d0a85f14d36a53fdd8ede2538fb
Source dataset
uspto-grants-2015_11
Patent number
US09193736B2

Reaction notes

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