2-Methyltetrahydrofuran → US9000184, 7, isomer 1

HRID 1468240노트

반응식

HRID 1468240 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.[Cl:25][C:26]1[CH:27]=[N:28][CH:29]=[C:30](B2OC(C)(C)C(C)(C)O2)[CH:31]=1.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>[Cl:25][C:26]1[CH:31]=[C:30]([C:2]2[CH:24]=[C:23]3[C:5]([CH2:6][CH2:7][C:8]4([C:16]53[N:20]=[C:19]([NH2:21])[C:18]([CH3:22])=[N:17]5)[CH2:9][CH2:10][CH:11]([O:14][CH3:15])[CH2:12][CH2:13]4)=[CH:4][CH:3]=2)[CH:29]=[N:28][CH:27]=1

참가 물질

9

반응물 5

HCID 73012-MethyltetrahydrofuranHCID 11430Potassium CarbonateHCID 231578663-Chloro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridineHCID 249491873-(Di-tert-butylphosphonium)propane sulfonateHCID 72714746US9000184, 5, isomer 1

생성물 1

HCID 72714841US9000184, 7, isomer 1

시약·촉매·용매 3

HCID 23938Palladium촉매HCID 178479786HCID 178479786, 화합물촉매HCID 962Water용매2회

반응 조건

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, 0.2 g, 0.51 mmol), 3-chloro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (123 mg, 0.51 mmol), 3-(di-tert-butylphosphonium)propane sulfonate (0.014 g, 0.05 mmol), sodium tetrachloropalladate(II) (7.54 mg, 0.03 mmol), 2-methyltetrahydrofuran (3 mL) and aq. potassium carbonate (2.0 M, 0.769 mL, 1.54 mmol) were added to microwave vial. The vial was sealed and heated in the 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. This procedure was repeated twice more. Water and 2-Me THF were added. The water phase was eliminated and the organic phase was washed once with brine and water. The organic phase was concentrated in vacuo. The product was purified using prep HPLC 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 water
  4. concentrationThe organic phase was concentrated in vacuo
  5. customThe product was purified
  6. customto give

출처 및 근거

ORD 기록
ord-48a7d74197bc4ce8bf9f7ba343716eec
출처 데이터셋
uspto-grants-2015_04
특허 번호
US09000184B2

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