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

HRID 659647Notes

Reaction equation

HRID 659647 reaction equation
[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

Participants

6

Reactant 2

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

Product 1

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

Reagents, catalysts & solvents 3

HCID 5003444Sodium cyanoborohydrideCatalystHCID 178460666HCID 178460666, compoundCatalystHCID 8028TetrahydrofuranSolvent

Procedure

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).

Workup

  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)

Sources & evidence

ORD record
ord-e9f9c9967e8649d2a5af06943e8af362
Source dataset
uspto-grants-2011_12
Patent number
US08080566B1

Reaction notes

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