1,4-Dioxane → Methyl 5-cyano-2,3'-bipyridine-6'-carboxylate

HRID 2098453Notes

Reaction equation

HRID 2098453 reaction equation
CC1(C)C(C)(C)OB([C:9]2[CH:10]=[CH:11][C:12]([C:15]([O:17][CH3:18])=[O:16])=[N:13][CH:14]=2)O1.Br[C:21]1[N:26]=[CH:25][C:24]([C:27]#[N:28])=[CH:23][CH:22]=1.C([O-])(O)=O.[Na+].O1CCOCC1>O.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].C(Cl)Cl>[C:27]([C:24]1[CH:23]=[CH:22][C:21]([C:9]2[CH:14]=[N:13][C:12]([C:15]([O:17][CH3:18])=[O:16])=[CH:11][CH:10]=2)=[N:26][CH:25]=1)#[N:28]

Participants

8

Reactant 4

HCID 312751,4-DioxaneHCID 516892Sodium BicarbonateHCID 50057186-Bromopyridine-3-carbonitrileHCID 467386632-Methoxycarbonyl-5-pyridineboronic acid, pinacol ester

Product 1

HCID 58286497Methyl 5-cyano-2,3'-bipyridine-6'-carboxylateYield 23%

Reagents, catalysts & solvents 3

HCID 178418807HCID 178418807, compoundCatalystHCID 962WaterSolvent2×HCID 6344DichloromethaneSolvent

Procedure

To a microwave vial was added methyl 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-pyridinecarboxylate (2 g, 7.60 mmol), 6-bromo-3-pyridinecarbonitrile (2.09 g, 11.40 mmol), PdCl2(dppf)-CH2Cl2 adduct (0.62 g, 0.760 mmol), NaHCO3 (1.277 g, 15.20 mmol), 1,4-dioxane (8 ml) and water (2 ml). The mixture was microwaved for 15 min at 105° C. The resulting dark solution was diluted with water and CH2Cl2. The aqueous layer was extracted three times with CH2Cl2. The CH2Cl2 extracts were passed over a phase separator, concentrated and purified on a Biotage SP4 with a 65i column at a flow rate of 65 ml/min, 0.1% TFA eluting with 2CV water, the 0-100% ACN/Water over 10 CV. The fractions containing the product were combined and diluted with CH2Cl2 and sat. NaHCO3. The layers were separated and the aqueous layer was extracted twice with CH2Cl2, then the combined organic extracts were dried and concentrated to afford the desired product (1.0 g, 1.75 mmol) as an off white solid. LCMS (m/z): 262.0 (M+Na).

Workup

  1. customThe mixture was microwaved for 15 min at 105° C
  2. extractionThe aqueous layer was extracted three times with CH2Cl2
  3. concentrationconcentrated
  4. custompurified on a Biotage SP4 with a 65i column at a flow rate of 65 ml/min, 0.1% TFA eluting with 2CV water
  5. additionThe fractions containing the product
  6. additiondiluted with CH2Cl2 and sat. NaHCO3
  7. customThe layers were separated
  8. extractionthe aqueous layer was extracted twice with CH2Cl2
  9. customthe combined organic extracts were dried
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-956ce52e5e644b5b86ce0aa44a1fe406
Source dataset
uspto-grants-2013_05
Patent number
US08450484B2

Reaction notes

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