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

HRID 1254447ノート

反応式

HRID 1254447 の反応式
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]

参加物

11

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 6

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 167845palladium(II) acetate触媒HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)触媒HCID 962Water溶媒HCID 8857Ethyl Acetate溶媒HCID 31374Dimethylacetamide溶媒

反応条件

温度
80 °C

実験手順

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)+.

後処理

  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)

出典と根拠

ORDレコード
ord-04273c676dc94257b47d258e1733f0d4
出典データセット
uspto-grants-2013_06
特許番号
US08455534B2

反応ノート

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