Methanesulfonic Acid → (5-Fluoro-4-methyl-pyrimidin-2-yl)-[3-methyl-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-amine

HRID 410406Notes

Reaction equation

HRID 410406 reaction equation
Cl[C:2]1[N:7]=[C:6]([CH3:8])[C:5]([F:9])=[CH:4][N:3]=1.[CH3:10][C:11]1[CH:12]=[C:13]([NH2:26])[CH:14]=[C:15]([B:17]2[O:21][C:20]([CH3:23])([CH3:22])[C:19]([CH3:25])([CH3:24])[O:18]2)[CH:16]=1.CS(O)(=O)=O>O1CCOCC1.C([O-])(O)=O.[Na+]>[F:9][C:5]1[C:6]([CH3:8])=[N:7][C:2]([NH:26][C:13]2[CH:14]=[C:15]([B:17]3[O:21][C:20]([CH3:22])([CH3:23])[C:19]([CH3:25])([CH3:24])[O:18]3)[CH:16]=[C:11]([CH3:10])[CH:12]=2)=[N:3][CH:4]=1

Participants

6

Reactant 3

HCID 6395Methanesulfonic AcidHCID 207780732-Chloro-5-fluoro-4-methylpyrimidineHCID 672361713-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline

Product 1

HCID 58456078(5-Fluoro-4-methyl-pyrimidin-2-yl)-[3-methyl-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-amineYield 62.6%

Reagents, catalysts & solvents 2

HCID 312751,4-DioxaneSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 2-chloro-5-fluoro-4-methyl-pyrimidine (4.00 g, 27.3 mmol) and 3-methyl-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenylamine (8.27 g, 35.5 mmol) in dioxane (40.7 mL) was added methanesulfonic acid (1.77 ml, 27.3 mmol) dropwise during which the reaction exothermed 15.7° C. Subsequently the reaction mixture was heated to 100° C. and allowed to stir over the weekend. The mixture was cooled to room temperature and was diluted with saturated aqueous NaHCO3 and extracted with ethyl acetate. The organic extracts were washed with brine and dried over MgSO4, filtered and concentrated in vacuo. Purification by flash chromatography provided (5-fluoro-4-methyl-pyrimidin-2-yl)-[3-methyl-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]amine (5.87 g, 17.1 mmol) MS ESI: [M+]+ m/z 344.1. 1H NMR (500 MHz, DMSO-d6) δ 9.50 (s, 1H), 8.38 (d, J=1.6, 1H), 7.81-7.62 (m, 2H), 7.07 (s, 1H), 2.36 (d, J=2.3, 3H), 2.26 (s, 3H), 1.27 (s, 12H).

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. extractionextracted with ethyl acetate
  3. washThe organic extracts were washed with brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customPurification by flash chromatography

Sources & evidence

ORD record
ord-b28512641b1246a9bf618a2ed2741058
Source dataset
uspto-grants-2014_06
Patent number
US08759366B2

Reaction notes

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