Nitrogen → 5-(But-1-yn-1-yl)-7-fluoro-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole

HRID 2069575노트

반응식

HRID 2069575 반응식
Br[C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([F:11])[CH:10]=1)[N:7]([CH:12]1[CH2:17][CH2:16][CH2:15][CH2:14][O:13]1)[N:6]=[CH:5]2.C([O-])([O-])=O.[K+].[K+].[C:24]([Si](C)(C)C)#[C:25][CH2:26][CH3:27].N#N>CCOC(C)=O.O.[Cu]I.CC([O-])=O.CC([O-])=O.[Pd+2].C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.[Fe+2].CC(N(C)C)=O>[C:24]([C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([F:11])[CH:10]=1)[N:7]([CH:12]1[CH2:17][CH2:16][CH2:15][CH2:14][O:13]1)[N:6]=[CH:5]2)#[C:25][CH2:26][CH3:27]

참가 물질

11

반응물 4

HCID 947NitrogenHCID 11430Potassium CarbonateHCID 439261-ButynyltrimethylsilaneHCID 667932045-bromo-7-fluoro-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole

생성물 1

HCID 667933445-(But-1-yn-1-yl)-7-fluoro-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole수율 52.2%

시약·촉매·용매 6

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)촉매HCID 167845palladium(II) acetate촉매HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)촉매HCID 962Water용매HCID 8857Ethyl Acetate용매HCID 31374Dimethylacetamide용매

반응 조건

온도
80 °C

실험 절차

Nitrogen was bubbled into a solution of 5-bromo-7-fluoro-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole (7.5 g, 25.33 mmol) and DMA (100 mL). After 5 min, CuI (241 mg, 1.27 mmol), Pd(OAc)2 (284 mg, 1.27 mmol), dppf (704 mg, 1.27 mmol), K2CO3 (4.89 g, 35.46 mmol), and but-1-yn-1-yltrimethylsilane (4.46 g, 35.46 mmol) were added sequentially with continued N2 bubbling. The resulting mixture was heated at 80° C. for 10 h under N2. The reaction mixture was diluted with EtOAc (250 mL) and H2O (200 mL) and filtered. The organic layer of the filtrate was separated, and the aqueous layer was extracted with EtOAc (2×100 mL). The combined organic layers were washed with brine (3×50 mL), dried over anhydrous Na2SO4, concentrated, and purified by silica gel chromatography (1:30 EtOAc/petroleum ether) to give the pure product as a yellow solid (3.6 g) and an impure product (2 g; further purified to give additional 1.47 g). 1H NMR (300 MHz, DMSO-d6): δ 8.19 (d, 1H), 7.68 (d, 1H), 7.26 (dd, 1H), 5.79 (dd, 1H), 3.92-3.87 (m, 1H), 3.69-3.60 (m, 1H), 2.47-2.34 (m, 1H), 2.43 (q, 2H), 2.07-2.02 (m, 2H), 1.76-1.69 (m, 1H), 1.57-1.50 (m, 2H), 1.17 (t, 3H); LCMS: 273 (M+H)+.

후처리

  1. filtrationfiltered
  2. customThe organic layer of the filtrate was separated
  3. extractionthe aqueous layer was extracted with EtOAc (2×100 mL)
  4. washThe combined organic layers were washed with brine (3×50 mL)
  5. dry with materialdried over anhydrous Na2SO4
  6. concentrationconcentrated
  7. custompurified by silica gel chromatography (1:30 EtOAc/petroleum ether)

출처 및 근거

ORD 기록
ord-c51711a3f65146588a3e2d17fc3d6f26
출처 데이터셋
uspto-grants-2012_10
특허 번호
US08299112B2

반응 노트

불러오는 중…