9-Ethyl-9H-carbazole-2-carbaldehyde → 2-((3-(1H-pyrazol-5-yl)piperidin-1-yl)methyl)-9-ethyl-9H-carbazole

HRID 659647노트

반응식

HRID 659647 반응식
[CH2:1]([N:3]1[C:15]2[CH:14]=[C:13]([CH:16]=O)[CH:12]=[CH:11][C:10]=2[C:9]2[C:4]1=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH3:2].Cl.[NH:19]1[C:23]([CH:24]2[CH2:29][CH2:28][CH2:27][NH:26][CH2:25]2)=[CH:22][CH:21]=[N:20]1>C1COCC1.CC(O[Ti](OC(C)C)(OC(C)C)OC(C)C)C.[BH3-]C#N.[Na+]>[NH:19]1[C:23]([CH:24]2[CH2:29][CH2:28][CH2:27][N:26]([CH2:16][C:13]3[CH:12]=[CH:11][C:10]4[C:9]5[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=5)[N:3]([CH2:1][CH3:2])[C:15]=4[CH:14]=3)[CH2:25]2)=[CH:22][CH:21]=[N:20]1

참가 물질

6

반응물 2

HCID 151341959-Ethyl-9H-carbazole-2-carbaldehydeHCID 534146693-(1H-Pyrazol-3-YL)piperidine hydrochloride

생성물 1

HCID 679961752-((3-(1H-pyrazol-5-yl)piperidin-1-yl)methyl)-9-ethyl-9H-carbazole수율 17%

시약·촉매·용매 3

HCID 5003444Sodium cyanoborohydride촉매HCID 178460666HCID 178460666, 화합물촉매HCID 8028Tetrahydrofuran용매

실험 절차

A 100-mL 3-necked round-bottom flask was charged with a solution of 9-ethyl-9H-carbazole-2-carbaldehyde (1.12 g, 5.02 mmol, 1.00 equiv) in THF (50 mL). To this was added 3-(1H-pyrazol-5-yl)piperidine hydrochloride (940 mg, 5.01 mmol, 1.00 equiv), Ti(OiPr)4 (2 g, 7.04 mmol, 1.40 equiv) and TEA (660 mg, 6.52 mmol, 1.30 equiv). The resulting solution was stirred at room temperature overnight. To the mixture was then added NaBH3CN (1.26 mg, 0.02 mmol, 4.00 equiv). The resulting solution was stirred at room temperature for 4 hours. Upon completion, the reaction was then quenched by the addition of water (50 mL). The resulting solution was extracted with ethyl acetate (4×50 mL) and the combined organic layers were dried over anhydrous magnesium sulfate and concentrated on a rotary evaporator. The residue was purified by silica gel column chromatography eluted with ethyl acetate/petroleum ether (1:10) affording 2-((3-(1H-pyrazol-5-yl)piperidin-1-yl)methyl)-9-ethyl-9H-carbazole as a white solid (0.3 g, 17%). LCMS:[M+H]+ 359. 1H NMR (CDCl3, 300 MHz) δ 8.08 (t, 2H), 7.50-7.41 (m, 4H), 7.28-7.21 (m, 2H), 6.05 (d, 1H), 4.40 (q, 2H), 3.80 (q, 2H), 3.16 (s, 1H), 2.72 (br, 4H), 1.88 (s, 1H), 1.65 (d, 3H), 1.46 (t, 3H).

후처리

  1. stirringThe resulting solution was stirred at room temperature for 4 hours
  2. customUpon completion, the reaction was then quenched by the addition of water (50 mL)
  3. extractionThe resulting solution was extracted with ethyl acetate (4×50 mL)
  4. dry with materialthe combined organic layers were dried over anhydrous magnesium sulfate
  5. concentrationconcentrated on a rotary evaporator
  6. customThe residue was purified by silica gel column chromatography
  7. washeluted with ethyl acetate/petroleum ether (1:10)

출처 및 근거

ORD 기록
ord-e9f9c9967e8649d2a5af06943e8af362
출처 데이터셋
uspto-grants-2011_12
특허 번호
US08080566B1

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