Dichloromethane → 5-(2-Formyl-8-morpholinoimidazo[1,2-a]pyrazin-5-yl)picolinonitrile

HRID 1772712Notes

Reaction equation

HRID 1772712 reaction equation
Br[C:2]1[N:7]2[CH:8]=[C:9]([CH:11]=[O: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.[C:19]([C:21]1[CH:26]=[CH:25][C:24](B2OC(C)(C)C(C)(C)O2)=[CH:23][N:22]=1)#[N:20].C(Cl)Cl>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]>[CH: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:24]3[CH:25]=[CH:26][C:21]([C:19]#[N:20])=[N:22][CH:23]=3)[N:7]2[CH:8]=1)=[O:12]

Participants

5

Reactant 3

HCID 6344DichloromethaneHCID 164141882-Cyanopyridine-5-boronic acid pinacol esterHCID 1177281135-Bromo-8-morpholinoimidazo[1,2-a]pyrazine-2-carbaldehyde

Product 1

HCID 1177284605-(2-Formyl-8-morpholinoimidazo[1,2-a]pyrazin-5-yl)picolinonitrile

Reagents, catalysts & solvents 1

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)Catalyst

Conditions

Temperature
90 °C

Procedure

Compound 2a (156 mg, 0.500 mmol), 2-cyanopyridine-5-boronic acid pinacol ester (230 mg, 1.00 mmol), and PdCl2(dppf).DCM (40.8 mg, 0.0500 mmol), were placed in an 8 mL vial equipped with a stir bar and then the vial was evacuated and backflushed with Argon gas. Dry DME (4 mL) and 2M Na2CO3 (2 mL) were added sequentially and then the reaction was stirred at 90° C. for 3 h. The reaction was cooled to rt and diluted with DCM (10 mL). The mixture was dried through a Na2SO4 pre-packed cartridge and then the solvent was removed under reduced pressure. The crude product was purified by flash column chromatography on silica gel (40-g SiO2 pre-packed column, 0-100% EtOAc/DCM) to afford compound 75a. 1H-NMR (400 MHz, CDCl3) δ (ppm): 10.08 (s, 1H), 8.93 (s, 1H), 8.17 (s, 1H), 8.02-8.10 (m, 1H), 7.88 (d, J=8.1 Hz, 1H), 7.49 (s, 1H), 4.47 (br. s., 4H), 3.90 (t, J=4.6 Hz, 4H). LCMS calcd for C17H14N6O2: 335.1 (M+H). found: 335.1.

Workup

  1. customvial equipped with a stir bar
  2. customthe vial was evacuated
  3. additionDry DME (4 mL) and 2M Na2CO3 (2 mL) were added sequentially
  4. temperatureThe reaction was cooled to rt
  5. additiondiluted with DCM (10 mL)
  6. dry with materialThe mixture was dried through a Na2SO4 pre-packed cartridge
  7. customthe solvent was removed under reduced pressure
  8. customThe crude product was purified by flash column chromatography on silica gel (40-g SiO2 pre-packed column, 0-100% EtOAc/DCM)

Sources & evidence

ORD record
ord-fa9d27b405a4475581ec25ac65bd2f47
Source dataset
uspto-grants-2016_02
Patent number
US09249163B2

Reaction notes

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