Nitrogen → tert-Butyl 5-(8-morpholino-2-(2-(quinolin-2-yl)ethynyl)imidazo[1,2-b]pyridazin-3-yl)pyridin-2-ylcarbamate

HRID 718620Notes

Reaction equation

HRID 718620 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.CC1(C)C(C)(C)OB([C:37]2[CH:38]=[CH:39][C:40]([NH:43][C:44](=[O:50])[O:45][C:46]([CH3:49])([CH3:48])[CH3:47])=[N:41][CH:42]=2)O1.N#N.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.O.CCOC(C)=O>[O:14]1[CH2:15][CH2:16][N:11]([C:10]2[C:5]3[N:6]([C:2]([C:37]4[CH:38]=[CH:39][C:40]([NH:43][C:44](=[O:50])[O:45][C:46]([CH3:48])([CH3:47])[CH3:49])=[N:41][CH:42]=4)=[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 947NitrogenHCID 10796Cesium carbonateHCID 17750222tert-butyl N-(5-(tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl)carbamateHCID 1177283744-(3-Bromo-2-(quinolin-2-ylethynyl)imidazo[1,2-b]pyridazin-8-yl)morpholine

Product 1

HCID 117732491tert-Butyl 5-(8-morpholino-2-(2-(quinolin-2-yl)ethynyl)imidazo[1,2-b]pyridazin-3-yl)pyridin-2-ylcarbamate

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 218864351,4-Dioxane--water (1/1)Solvent

Conditions

Temperature
85 °C

Procedure

A solution of compound 18b (0.50 g, 1.2 mmol) and tert-butyl 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-ylcarbamate (0.44 g, 1.4 mmol) in dioxane/water (4:1 v/v, 5 mL) was purged with N2. Dichloro(diphenylphosphinoferrocene)palladium (42 mg, 0.06 mmol) was then added, followed by solid Cs2CO3 (0.94 g, 2.9 mmol). The reaction mixture was stirred at 85° C. for 1 h under N2, and allowed to cool to rt. EtOAc (100 mL) was then added. The organic layer was washed with water (2×50 mL), and brine (100 mL), dried over Na2SO4, filtered and concentrated to give a residue which was purified by flash column chromatography on silica gel (0-40% EtOAc/heptanes) to give compound 38a as a yellow solid. Mass Spectrum (LCMS, ESI pos.): Calcd. for C31H29N7O3: 548.2 (M+H). found: 548.1.

Workup

  1. temperatureto cool to rt
  2. washThe organic layer was washed with water (2×50 mL), and brine (100 mL)
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto give a residue which
  7. customwas purified by flash column chromatography on silica gel (0-40% EtOAc/heptanes)

Sources & evidence

ORD record
ord-83cb8282ff8d40eda7fb23488aca7047
Source dataset
uspto-grants-2015_11
Patent number
US09193736B2

Reaction notes

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