2-Methyltetrahydrofuran → US9000184, 6, isomer 1

HRID 1468239노트

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HRID 1468239 반응식
Br[C:2]1[CH:24]=[C:23]2[C:5]([CH2:6][CH2:7][C:8]3([C:16]42[N:20]=[C:19]([NH2:21])[C:18]([CH3:22])=[N:17]4)[CH2:13][CH2:12][CH:11]([O:14][CH3:15])[CH2:10][CH2:9]3)=[CH:4][CH:3]=1.[CH3:25][O:26][C:27]1[CH:28]=[C:29]([CH:32]=[C:33](B2OC(C)(C)C(C)(C)O2)[CH:34]=1)[C:30]#[N:31].CC([PH+](C(C)(C)C)CCCS([O-])(=O)=O)(C)C.CC1CCCO1.C(=O)([O-])[O-].[K+].[K+]>[Na+].[Na+].Cl[Pd+2](Cl)(Cl)Cl.[Pd].O>[NH2:21][C:19]1[C:18]([CH3:22])=[N:17][C:16]2([C:23]3[C:5](=[CH:4][CH:3]=[C:2]([C:33]4[CH:32]=[C:29]([CH:28]=[C:27]([O:26][CH3:25])[CH:34]=4)[C:30]#[N:31])[CH:24]=3)[CH2:6][CH2:7][C:8]32[CH2:9][CH2:10][CH:11]([O:14][CH3:15])[CH2:12][CH2:13]3)[N:20]=1

참가 물질

9

반응물 5

HCID 73012-MethyltetrahydrofuranHCID 11430Potassium CarbonateHCID 249491873-(Di-tert-butylphosphonium)propane sulfonateHCID 467393223-Methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzonitrileHCID 72714746US9000184, 5, isomer 1

생성물 1

HCID 72714747US9000184, 6, isomer 1

시약·촉매·용매 3

HCID 23938Palladium촉매HCID 178479786HCID 178479786, 화합물촉매HCID 962Water용매2회

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온도
130 °C

실험 절차

7′-Bromo-4-methoxy-5″-methyl-3′,4′-dihydrodispiro[cyclohexane-1,2′-naphthalene-1′,2″-imidazol]-4″-amine (Example 5, 0.184 g, 0.47 mmol), 3-methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzonitrile (0.122 g, 0.47 mmol), 3-(di-tert-butylphosphonium)propane sulfonate (0.013 g, 0.05 mmol), sodium tetrachloropalladate(II) (6.95 mg, 0.02 mmol), 2-methyltetrahydrofuran (3 mL) and potassium carbonate (2.0 M, 0.708 mL, 1.42 mmol) were added to a microwave vial. The vial was sealed and heated with MW for 30 min at 130° C. The same amount of ligand and Pd-catalyst were added again and the reaction was heated in the MW for 15 min at 130° C. Water and 2-Me THF was added and the water phase was eliminated. The organic phase was washed once with brine and once with water. The organic phase was concentrated in vacuo. The product was purified using prep HPLC. Fractions containing the isomeric products were collected separately and the MeOH was evaporated. DCM was added and the mixture was poured into a phase separator. The organic phase was concentrated in vacuo to give:

후처리

  1. customThe vial was sealed
  2. temperaturethe reaction was heated in the MW for 15 min at 130° C
  3. washThe organic phase was washed once with brine and once with water
  4. concentrationThe organic phase was concentrated in vacuo
  5. customThe product was purified
  6. additionFractions containing the isomeric products
  7. customwere collected separately
  8. customthe MeOH was evaporated
  9. additionDCM was added
  10. additionthe mixture was poured into a phase separator
  11. concentrationThe organic phase was concentrated in vacuo
  12. customto give

출처 및 근거

ORD 기록
ord-7dc2a86c95d54fa3ad825d9aeb760a3c
출처 데이터셋
uspto-grants-2015_04
특허 번호
US09000184B2

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