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

HRID 1039885Notes

Reaction equation

HRID 1039885 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:6]=[C:7]([B:9]2[O:13][C:12]([CH3:15])([CH3:14])[C:11]([CH3:17])([CH3:16])[O:10]2)[CH:8]=1)[NH2:5].Cl[C:19]1[N:24]=[C:23]([C:25]([F:28])([F:27])[F:26])[CH:22]=[CH:21][N:20]=1.O1CCOCC1.CS(O)(=O)=O>C(OCC)(=O)C>[F:1][C:2]1[CH:3]=[C:4]([NH:5][C:19]2[N:24]=[C:23]([C:25]([F:28])([F:27])[F:26])[CH:22]=[CH:21][N:20]=2)[CH:6]=[C:7]([B:9]2[O:13][C:12]([CH3:15])([CH3:14])[C:11]([CH3:17])([CH3:16])[O:10]2)[CH:8]=1

Participants

6

Reactant 4

HCID 6395Methanesulfonic AcidHCID 312751,4-DioxaneHCID 27739122-Chloro-4-(trifluoromethyl)pyrimidineHCID 597700393-Fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline

Product 1

HCID 58456086N-[3-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-4-(trifluoromethyl)pyrimidin-2-amineYield 76.4%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

To a flask containing 3-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (3.3 g, 14.00 mmol) and 2-chloro-4-(trifluoromethyl)pyrimidine (2.94 g, 16.10 mmol) were added dioxane (44 mL) and methanesulfonic acid (1.55 g, 16.10 mmol) and the reaction was heated at 100° C. overnight. The reaction was cooled, diluted with ethyl acetate, washed with water, dried over magnesium sulfate, filtered and concentrated. Flash chromatography was used for purification to yield. N-[3-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-4-(trifluoromethyl)pyrimidin-2-amine (4.10 g, 10.70 mmol, 76% yield). MS ESI: [M+H]+ m/z 384. 1H NMR (500 MHz, DMSO-d6) δ 10.41 (s, 1H), 8.85 (d, J=4.9, 1H), 7.92 (dt, J=2.3, 12.1, 1H), 7.77 (d, J=1.5, 1H), 7.32 (d, J=4.9, 1H), 6.98 (dd, J=2.2, 8.4, 1H), 1.28 (s, 12H).

Workup

  1. temperatureThe reaction was cooled
  2. washwashed with water
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customFlash chromatography was used for purification
  7. customto yield

Sources & evidence

ORD record
ord-e72268150fa845b4b7bb972bfba3674c
Source dataset
uspto-grants-2013_10
Patent number
US08551984B2

Reaction notes

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