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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 1039896
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HRID 1039896 반응식
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
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6

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

생성물 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]-amine수율 62.6%

시약·촉매·용매 2

HCID 312751,4-Dioxane
용매
HCID 516892Sodium Bicarbonate용매

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온도
100 °C

실험 절차

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+H]+ m/z 344.1. 1H NMR (500 MHz, DMSO-d6) δ 9.50 (s, 1H), 838 (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).

후처리

  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

출처 및 근거

ORD 기록
ord-d6a3f5970a0449208fef03f18bbfd0bc
출처 데이터셋
uspto-grants-2013_10
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08551984B2

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