Cesium carbonate → 5-(2-(Hydroxymethyl)-8-morpholinoimidazo[1,2-a]pyrazin-5-yl)picolinonitrile

HRID 1772588Notes

Reaction equation

HRID 1772588 reaction equation
Br[C:2]1[N:7]2[CH:8]=[C:9]([CH2:11][OH:12])[N:10]=[C:6]2[C:5]([N:13]2[CH2:18][CH2:17][O:16][CH2:15][CH2:14]2)=[N:4][CH:3]=1.CC1(C)C(C)(C)OB([C:27]2[CH:28]=[CH:29][C:30]([C:33]#[N:34])=[N:31][CH:32]=2)O1.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.O.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.Cl[Pd]Cl.[Fe+2]>[OH:12][CH2:11][C:9]1[N:10]=[C:6]2[C:5]([N:13]3[CH2:18][CH2:17][O:16][CH2:15][CH2:14]3)=[N:4][CH:3]=[C:2]([C:27]3[CH:28]=[CH:29][C:30]([C:33]#[N:34])=[N:31][CH:32]=3)[N:7]2[CH:8]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 164141882-Cyanopyridine-5-boronic acid pinacol esterHCID 117727888(5-Bromo-8-morpholinoimidazo[1,2-a]pyrazin-2-yl)methanol

Product 1

HCID 1177279105-(2-(Hydroxymethyl)-8-morpholinoimidazo[1,2-a]pyrazin-5-yl)picolinonitrileYield 54.2%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 218864351,4-Dioxane--water (1/1)Solvent

Conditions

Temperature
90 °C

Procedure

To a solution of compound 1e (600 mg, 1.92 mmol, as prepared in Step E) in 1,4-dioxane/H2O (4:1 v/v, 8 mL) was added compound 1f (560 mg, 2.44 mmol), PdCl2(dppf) (72.1 mg, 0.0960 mmol) and Cs2CO3 (847 mg, 4.99 mmol). The reaction mixture was stirred at 90° C. for 2 h under a nitrogen atmosphere. After cooling to rt, the reaction was quenched with H2O (20 mL). The resulting mixture was extracted with DCM (2×50 mL). The combined organic layers were dried over Na2SO4, filtered, and concentrated under reduced pressure. The resulting residue was purified by flash column chromatography on silica gel with EtOAc/petroleum ether (1:2 v/v) to obtain compound 1g as a yellow solid (350 mg, 51% yield). Mass Spectrum (LCMS, ESI pos.): Calcd. for C17H16N6O2: 337.1 (M+H). Found 337.2.

Workup

  1. temperatureAfter cooling to rt
  2. customthe reaction was quenched with H2O (20 mL)
  3. extractionThe resulting mixture was extracted with DCM (2×50 mL)
  4. dry with materialThe combined organic layers were dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe resulting residue was purified by flash column chromatography on silica gel with EtOAc/petroleum ether (1:2 v/v)

Sources & evidence

ORD record
ord-1ffa3dcbae01441b8b03c509c18cc98d
Source dataset
uspto-grants-2016_02
Patent number
US09249163B2

Reaction notes

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