(4-Cyano-3-fluorophenyl)boronic acid → HCID 58504701, compound

HRID 2367525Notes

Reaction equation

HRID 2367525 reaction equation
Cl[C:2]1[CH:7]=[C:6]([N:8]2[C@H:13]([CH3:14])[CH2:12][O:11][C@H:10]([CH2:15][N:16]([CH3:18])[CH3:17])[CH2:9]2)[N:5]=[C:4]([NH:19][CH3:20])[N:3]=1.[C:21]([C:23]1[CH:28]=[CH:27][C:26](B(O)O)=[CH:25][C:24]=1[F:32])#[N:22]>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>[CH3:17][N:16]([CH2:15][C@H:10]1[O:11][CH2:12][C@@H:13]([CH3:14])[N:8]([C:6]2[N:5]=[C:4]([NH:19][CH3:20])[N:3]=[C:2]([C:26]3[CH:27]=[CH:28][C:23]([C:21]#[N:22])=[C:24]([F:32])[CH:25]=3)[CH:7]=2)[CH2:9]1)[CH3:18]

Participants

6

Reactant 2

HCID 2783130(4-Cyano-3-fluorophenyl)boronic acidHCID 58504442HCID 58504442, compound

Product 1

HCID 58504701HCID 58504701, compoundYield 85%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
100 °C

Procedure

A mixture of 4-chloro-6-{(2R,5R)-2-[(dimethylamino)methyl]-5-methyl-4-morpholinyl}-N-methyl-2-pyrimidinamine (60 mg, 0.20 mmol), (4-cyano-3-fluorophenyl)boronic acid (73 mg, 0.44 mmol), and Pd(PPh3)4 (12 mg, 0.010 mmol) in 1,4-dioxane (2 mL) and saturated aqueous NaHCO3 (1 mL) was degassed with nitrogen for 10 minutes. The vial was then capped and stirred at 100° C. for 15 hours. The mixture was cooled, diluted with saturated aqueous NaHCO3 (5 mL) and water (5 mL), and extracted with EtOAc (2×10 mL). The extracts were washed with brine (10 mL), dried (Na2SO4), filtered, and concentrated in vacuo. The residue was purified by flash chromatography (10 g SiO2, CH2Cl2 to 95/5/0.5 CH2Cl2/CH3OH/NH4OH gradient) to give the title compound (58 mg, about 85% purity) as a yellow oil. LC-MS (ES) m/z=385 [M+H]+.

Workup

  1. customwas degassed with nitrogen for 10 minutes
  2. customThe vial was then capped
  3. temperatureThe mixture was cooled
  4. additiondiluted with saturated aqueous NaHCO3 (5 mL) and water (5 mL)
  5. extractionextracted with EtOAc (2×10 mL)
  6. washThe extracts were washed with brine (10 mL)
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe residue was purified by flash chromatography (10 g SiO2, CH2Cl2 to 95/5/0.5 CH2Cl2/CH3OH/NH4OH gradient)

Sources & evidence

ORD record
ord-232fc8e14b36473486e9b307288234b8
Source dataset
uspto-grants-2014_04
Patent number
US08697685B2

Reaction notes

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