Dimethylformamide → 4-(3-Bromo-2-(quinolin-2-ylethynyl)imidazo[1,2-b]pyridazin-8-yl)morpholine

HRID 718586

Reaction equation

HRID 718586 reaction equation
[Br:1][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]#[CH:18].Br[C:20]1[CH:29]=[CH:28][C:27]2[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=2)[N:21]=1.CN(C=O)C.CCN(C(C)C)C(C)C>[Cu]I.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O>[Br:1][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:20]1[CH:29]=[CH:28][C:27]2[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=2)[N:21]=1

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 81531DiisopropylethylamineHCID 27627562-BromoquinolineHCID 1177287753-Bromo-2-ethynyl-8-(4-morpholinyl)imidazo[1,2-b]pyridazine

Product 1

HCID 1177283744-(3-Bromo-2-(quinolin-2-ylethynyl)imidazo[1,2-b]pyridazin-8-yl)morpholine

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolvent

Procedure

A mixture of compound 18a (0.74 g, 2.4 mmol) and 2-bromoquinoline (2.0 g, 9.6 mmol) in a vial was evacuated and back-flushed with Argon. Dry DMF (10 mL) and DIEA (1.7 mL, 9.7 mmol) were added via syringe and the mixture was deoxygenated by bubbling Argon through the stirred solution for 5 min. To the mixture was added CuI (46 mg, 0.24 mmol) and dichlorobis(triphenylphosphine)palladium(II) (0.17 g, 0.24 mmol). The reaction mixture was stirred at rt overnight, and was poured into water (50 mL). The mixture was extracted with EtOAc (3×30 mL). The combined organic extracts were washed with water (20 mL) and brine (20 mL), and dried over Na2SO4. The mixture was filtered, and the filtrate was concentrated to obtain a residue which was purified by flash column chromatography on silica gel (30-70% EtOAc/heptane) to obtain compound 18b as a white solid. Mass Spectrum (LCMS, ESI pos.): Calcd. for C21H16BrN5O: 434.1 (M+H). found: 434.2.

Workup

  1. customwas evacuated
  2. customback-flushed with Argon
  3. customthe mixture was deoxygenated
  4. customby bubbling Argon through the stirred solution for 5 min
  5. extractionThe mixture was extracted with EtOAc (3×30 mL)
  6. washThe combined organic extracts were washed with water (20 mL) and brine (20 mL)
  7. dry with materialdried over Na2SO4
  8. filtrationThe mixture was filtered
  9. concentrationthe filtrate was concentrated
  10. customto obtain a residue which
  11. customwas purified by flash column chromatography on silica gel (30-70% EtOAc/heptane)

Sources & evidence

ORD record
ord-14aa77af36e84f828a7b05a70fc52a24
Source dataset
uspto-grants-2015_11
Patent number
US09193736B2

Linked notes

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