(4-Cyano-3-fluorophenyl)boronic acid → HCID 58504779, compound

HRID 2367516Notes

Reaction equation

HRID 2367516 reaction equation
Cl[C:2]1[N:7]=[C:6]([NH:8][CH3:9])[N:5]=[C:4]([N:10]2[C@H:15]([CH3:16])[CH2:14][O:13][C@H:12]([CH2:17][OH:18])[CH2:11]2)[CH:3]=1.[C:19]([C:21]1[CH:26]=[CH:25][C:24](B(O)O)=[CH:23][C:22]=1[F:30])#[N:20]>O1CCOCC1.C([O-])(O)=O.[Na+].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>[F:30][C:22]1[CH:23]=[C:24]([C:2]2[CH:3]=[C:4]([N:10]3[C@H:15]([CH3:16])[CH2:14][O:13][C@H:12]([CH2:17][OH:18])[CH2:11]3)[N:5]=[C:6]([NH:8][CH3:9])[N:7]=2)[CH:25]=[CH:26][C:21]=1[C:19]#[N:20]

Participants

6

Reactant 2

HCID 2783130(4-Cyano-3-fluorophenyl)boronic acidHCID 51353726HCID 51353726, compound

Product 1

HCID 58504779HCID 58504779, compoundYield 91.2%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of {(2S,5R)-4-[6-chloro-2-(methylamino)-4-pyrimidinyl]-5-methyl-2-morpholinyl}methanol (2.24 g, 7.24 mmol), (4-cyano-3-fluorophenyl)boronic acid (2.64 g, 16.01 mmol), and Pd(PPh3)4 (0.43 g, 0.37 mmol) in 1,4-dioxane (50 mL) and saturated aqueous NaHCO3 (25 mL) was degassed with nitrogen for 10 minutes. It was then stirred at 100° C. under nitrogen for 17 hours, cooled, diluted with water (25 mL) and saturated aqueous NaHCO3 (100 mL), and extracted with EtOAc (3×100 mL). The extracts were washed with brine (150 mL), dried (Na2SO4), filtered, and concentrated in vacuo. The residue was purified by flash chromatography (90 g SiO2, 20-100% EtOAc in hexanes gradient) to give the title compound (2.36 g) as a yellow solid. LC-MS (ES) m/z=358 [M+H]+.

Workup

  1. customwas degassed with nitrogen for 10 minutes
  2. temperaturecooled
  3. additiondiluted with water (25 mL) and saturated aqueous NaHCO3 (100 mL)
  4. extractionextracted with EtOAc (3×100 mL)
  5. washThe extracts were washed with brine (150 mL)
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by flash chromatography (90 g SiO2, 20-100% EtOAc in hexanes gradient)

Sources & evidence

ORD record
ord-b9f2c7556d2f49d0a0dce39da6909771
Source dataset
uspto-grants-2014_04
Patent number
US08697685B2

Reaction notes

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