Nitrogen → (E)-Methyl 4-(8-morpholino-2-(2-(5,6,7,8-tetrahydroquinolin-2-yl)vinyl)imidazo[1,2-b]pyridazin-3-yl)benzoate

HRID 718668Notes

Reaction equation

HRID 718668 reaction equation
[N:1]1[C:10]2[CH2:9][CH2:8][CH2:7][CH2:6][C:5]=2[CH:4]=[CH:3][C:2]=1[CH2:11]P(=O)(OCC)OCC.N#N.[Li]CCCC.[CH:27]([C:29]1[N:30]=[C:31]2[C:36]([N:37]3[CH2:42][CH2:41][O:40][CH2:39][CH2:38]3)=[CH:35][CH:34]=[N:33][N:32]2[C:43]=1[C:44]1[CH:53]=[CH:52][C:47]([C:48]([O:50][CH3:51])=[O:49])=[CH:46][CH:45]=1)=O>C1COCC1>[O:40]1[CH2:39][CH2:38][N:37]([C:36]2[C:31]3[N:32]([C:43]([C:44]4[CH:53]=[CH:52][C:47]([C:48]([O:50][CH3:51])=[O:49])=[CH:46][CH:45]=4)=[C:29](/[CH:27]=[CH:11]/[C:2]4[CH:3]=[CH:4][C:5]5[CH2:6][CH2:7][CH2:8][CH2:9][C:10]=5[N:1]=4)[N:30]=3)[N:33]=[CH:34][CH:35]=2)[CH2:42][CH2:41]1

Participants

6

Reactant 4

HCID 947NitrogenHCID 117728372Methyl 4-(2-formyl-8-morpholinoimidazo[1,2-b]pyridazin-3-yl)benzoateHCID 117732512Diethyl (5,6,7,8-tetrahydroquinolin-2-yl-methyl)phosphonateHCID 178418339Butyllithium

Product 1

HCID 117732515(E)-Methyl 4-(8-morpholino-2-(2-(5,6,7,8-tetrahydroquinolin-2-yl)vinyl)imidazo[1,2-b]pyridazin-3-yl)benzoate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of compound 58b (0.70 g, 2.5 mmol) in THF (15 mL) was purged with N2. n-BuLi (2.5 M in hexane, 1.1 mL, 2.8 mmol) was added dropwise with stirring at rt and allowed to stir for 1 h. To the mixture was added compound 58c (0.70 g, 1.9 mmol). The resulting mixture was stirred overnight at rt, and quenched with saturated NH4Cl solution (100 mL). The resulting solution was extracted with DCM (3×100 mL). The combined organic layers were dried over Na2SO4, filtered and concentrated under reduced pressure. The residue obtained was purified by flash column chromatography on silica gel (EtOAc/petroleum ether (1:2 v/v)) to obtain compound 58d as a white solid. Mass Spectrum (LCMS, ESI pos.): Calcd. for C29H29N5O3: 496.2 (M+H). Found: 496.2.

Workup

  1. stirringto stir for 1 h
  2. stirringThe resulting mixture was stirred overnight at rt
  3. customquenched with saturated NH4Cl solution (100 mL)
  4. extractionThe resulting solution was extracted with DCM (3×100 mL)
  5. dry with materialThe combined organic layers were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue obtained
  9. customwas purified by flash column chromatography on silica gel (EtOAc/petroleum ether (1:2 v/v))

Sources & evidence

ORD record
ord-441d732b7855463fb9c21668dad0845e
Source dataset
uspto-grants-2015_11
Patent number
US09193736B2

Reaction notes

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