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

HRID 410401Notes

Reaction equation

HRID 410401 reaction equation
Cl[C:2]1[N:7]=[C:6]([CH2:8][CH3:9])[CH:5]=[CH:4][N:3]=1.[CH3:10][C:11]1[CH:12]=[C:13]([CH:15]=[C:16]([B:18]2[O:22][C:21]([CH3:24])([CH3:23])[C:20]([CH3:26])([CH3:25])[O:19]2)[CH:17]=1)[NH2:14].CS(O)(=O)=O>O1CCOCC1.C(OCC)(=O)C>[CH2:8]([C:6]1[CH:5]=[CH:4][N:3]=[C:2]([NH:14][C:13]2[CH:15]=[C:16]([B:18]3[O:22][C:21]([CH3:23])([CH3:24])[C:20]([CH3:26])([CH3:25])[O:19]3)[CH:17]=[C:11]([CH3:10])[CH:12]=2)[N:7]=1)[CH3:9]

Participants

6

Reactant 3

HCID 6395Methanesulfonic AcidHCID 157830262-Chloro-4-ethylpyrimidine2×HCID 672361713-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline

Product 1

HCID 584563724-ethyl-N-[3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]pyrimidin-2-amine

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

A solution of 2-chloro-4-ethyl pyrimidine (0.98 g, 7.00 mmol), the product of Step 1 (1.794 g, 7.70 mmol), and methanesulfonic acid (0.50 mL, 7.70 mmol) in 1,4-dioxane (30 mL) was sealed in a 100 mL screw-top pressure flask and heated at 110° C. for 15 hours. The flask was cooled, an additional portion of 2-chloro-4-ethyl pyrimidine (0.145 g, 1.05 mmol) was added, and the flask was resealed and heated for another 6.5 hours. The reaction mixture was cooled, diluted with ethyl acetate (70 mL), washed with saturated aqueous sodium bicarbonate solution (25 mL) and brine (25 mL), dried over sodium sulfate, filtered, and concentrated. The resulting reddish brown solid 4-ethyl-N-[3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]pyrimidin-2-amine (3.44 g as a 80:20 w/w mixture with 1,4-dioxane) was used without further purification. MS ESI: [M+H]+ m/z 340.1

Workup

  1. temperatureThe flask was cooled
  2. temperatureheated for another 6.5 hours
  3. temperatureThe reaction mixture was cooled
  4. washwashed with saturated aqueous sodium bicarbonate solution (25 mL) and brine (25 mL)
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe resulting reddish brown solid 4-ethyl-N-[3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]pyrimidin-2-amine (3.44 g as a 80:20 w/w mixture with 1,4-dioxane) was used without further purification

Sources & evidence

ORD record
ord-bc96e29404714caba08806a6fb82fb7e
Source dataset
uspto-grants-2014_06
Patent number
US08759366B2

Reaction notes

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