Cesium fluoride → 6-Methyl-3-(2-pyrimidinyl)-2-pyridinecarbonitrile

HRID 1094758Notes

Reaction equation

HRID 1094758 reaction equation
CC1(C)COB([C:8]2[C:9]([C:15]#[N:16])=[N:10][C:11]([CH3:14])=[CH:12][CH:13]=2)OC1.Br[C:19]1[N:24]=[CH:23][CH:22]=[CH:21][N:20]=1.[F-].[Cs+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Cu]I.O1CCOCC1>[CH3:14][C:11]1[N:10]=[C:9]([C:15]#[N:16])[C:8]([C:19]2[N:24]=[CH:23][CH:22]=[CH:21][N:20]=2)=[CH:13][CH:12]=1

Participants

7

Reactant 3

HCID 25953Cesium fluorideHCID 783452-BromopyrimidineHCID 593637323-(5,5-Dimethyl-1,3,2-dioxaborinan-2-yl)-6-methyl-2-pyridinecarbonitrile

Product 1

HCID 593637436-Methyl-3-(2-pyrimidinyl)-2-pyridinecarbonitrile

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
65 °C

Procedure

An alternative route to make D18 is: 3-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-6-methyl-2-pyridinecarbonitrile D17 (50.6 mg) was dissolved 1,4-Dioxane (1 ml) under nitrogen in a vial, then 2-bromopyrimidine (42.0 mg, 0.264 mmol), CsF (67 mg, 0.441 mmol), Pd(Ph3P)4 (12 mg, 10.38 μmol) and CuI (7 mg, 0.037 mmol) were added in sequence. The vial was then capped and stirred at 65° C., after 1 hour the solvent was removed at reduced pressure and the residue partitioned between AcOEt (10 mls) and NaHCO3 (saturated solution, 10 ml). The phases were separated and the water was extracted with AcOEt (2×10 mls). The organic fraction were joined together, dried over Na2SO4 and evaporated at reduced pressure, obtaining an orange oily residue which was purified (Biotage, Snap 25 g silica gel column, AcOEt/Cy from pure Cy to 50:50 in 10 column volumes) to obtain the title compound D18 as pale yellow solid (27.6 mg).

Workup

  1. additionwere added in sequence
  2. customThe vial was then capped
  3. customwas removed at reduced pressure
  4. customthe residue partitioned between AcOEt (10 mls) and NaHCO3 (saturated solution, 10 ml)
  5. customThe phases were separated
  6. extractionthe water was extracted with AcOEt (2×10 mls)
  7. dry with materialdried over Na2SO4
  8. customevaporated at reduced pressure
  9. customobtaining an orange oily residue which
  10. customwas purified (Biotage, Snap 25 g silica gel column, AcOEt/Cy from pure Cy to 50:50 in 10 column volumes)

Sources & evidence

ORD record
ord-811bd4e2c48b44559a7e26814be9fd4f
Source dataset
uspto-grants-2012_03
Patent number
US08133908B2

Reaction notes

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