1,4-Dioxane → 4-[2-Amino-6-(phenylamino)-4-pyrimidinyl]-2-fluorobenzonitrile

HRID 2367172노트

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HRID 2367172 반응식
[C:1]([C:3]1[CH:8]=[CH:7][C:6](B(O)O)=[CH:5][C:4]=1[F:12])#[N:2].Cl[C:14]1[N:19]=[C:18]([NH2:20])[N:17]=[C:16]([NH:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH:15]=1.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.O>[NH2:20][C:18]1[N:19]=[C:14]([C:6]2[CH:7]=[CH:8][C:3]([C:1]#[N:2])=[C:4]([F:12])[CH:5]=2)[CH:15]=[C:16]([NH:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[N:17]=1

참가 물질

7

반응물 4

HCID 312751,4-DioxaneHCID 516892Sodium BicarbonateHCID 14842836-chloro-N4-phenylpyrimidine-2,4-diamineHCID 2783130(4-Cyano-3-fluorophenyl)boronic acid

생성물 1

HCID 513565894-[2-Amino-6-(phenylamino)-4-pyrimidinyl]-2-fluorobenzonitrile수율 99.9%

시약·촉매·용매 2

HCID 178418397HCID 178418397, 화합물촉매HCID 962Water용매

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온도
100 °C

실험 절차

To (4-cyano-3-fluorophenyl)boronic acid (197 mg, 1.20 mmol) and 6-chloro-N4-phenyl-2,4-pyrimidinediamine (330 mg, 1.50 mmol) in a sealable flask were added 1,4-dioxane (6 mL) and saturated aqueous NaHCO3 (3 mL). The mixture was degassed with nitrogen gas for 10 minutes. Pd(Ph3P)4 (86 mg, 0.075 mmol) was added and the reaction mixture was stirred overnight at 100° C. The mixture was poured onto EtOAc and water. The organic layer was separated and the aqueous layer was further extracted with EtOAc. The combined organic layers were washed with brine, dried (MgSO4), filtered and concentrated. The resulting residue was chromatographed on SiO2 (gradient: 99:1:0.1 CHCl3/CH3OH/NH4OH to 90:10:1 CHCl3/CH3OH/NH4OH) to afford the title compound (366 mg). LC-MS (ES) m/z=306 [M+H]+.

후처리

  1. customThe mixture was degassed with nitrogen gas for 10 minutes
  2. customThe organic layer was separated
  3. extractionthe aqueous layer was further extracted with EtOAc
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe resulting residue was chromatographed on SiO2 (gradient: 99:1:0.1 CHCl3/CH3OH/NH4OH to 90:10:1 CHCl3/CH3OH/NH4OH)

출처 및 근거

ORD 기록
ord-5a405296c1464bdaa02da2d070b049cb
출처 데이터셋
uspto-grants-2014_04
특허 번호
US08697685B2

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