Dichloromethane → 3-((3-(1H-pyrazol-5-yl)piperidin-1-yl)methyl)-9-ethyl-9H-carbazole

HRID 659607Notes

Reaction equation

HRID 659607 reaction equation
[NH:1]1[C:5]([CH:6]2[CH2:11][CH2:10][CH2:9][NH:8][CH2:7]2)=[CH:4][CH:3]=[N:2]1.[CH2:12]([N:14]1[C:26]2[CH:25]=[C:24](C=O)[CH:23]=[CH:22][C:21]=2[C:20]2[C:15]1=[CH:16][CH:17]=[CH:18][CH:19]=2)[CH3:13].[BH3-][C:30]#N.[Na+].C(Cl)Cl>O1CCCC1.CC(O[Ti](OC(C)C)(OC(C)C)OC(C)C)C.CO>[NH:1]1[C:5]([CH:6]2[CH2:11][CH2:10][CH2:9][N:8]([CH2:30][C:23]3[CH:24]=[CH:25][C:26]4[N:14]([CH2:12][CH3:13])[C:15]5[C:20]([C:21]=4[CH:22]=3)=[CH:19][CH:18]=[CH:17][CH:16]=5)[CH2:7]2)=[CH:4][CH:3]=[N:2]1

Participants

8

Reactant 4

HCID 6344DichloromethaneHCID 5003444Sodium cyanoborohydrideHCID 151341959-Ethyl-9H-carbazole-2-carbaldehydeHCID 429613013-(1H-pyrazol-5-yl)piperidine

Product 1

HCID 451784693-((3-(1H-pyrazol-5-yl)piperidin-1-yl)methyl)-9-ethyl-9H-carbazoleYield 5.2%

Reagents, catalysts & solvents 3

HCID 178460666HCID 178460666, compoundCatalystHCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

A 100-mL 3-necked round-bottom flask was charged with a solution of 3-(1H-pyrazol-5-yl)piperidine (1.8 g, 11.31 mmol, 1.00 equiv, 95%) in tetrahydrofuran (THF) (100 mL). To this was added 9-ethyl-9H-carbazole-2-carbaldehyde (2.66 g, 11.32 mmol, 1.02 equiv, 95%) and Ti(OiPr)4 (4.24 g, 14.76 mmol, 1.25 equiv, 99%). The resulting solution was allowed to stir at room temperature overnight. To the mixture was then added NaBH3CN (3 g, 47.26 mmol, 4.00 equiv, 99%). The resulting mixture was allowed to stir at room temperature overnight. The progress was monitored by TLC (DCM; MeOH=10:1). Upon completion, the reaction was quenched by the addition of saturated aqueous Na2CO3 (150 mL). The resulting mixture was extracted with ethyl acetate (5×200 mL). Combined organic layers were dried over MgSO4, filtered off and concentrated on a rotary evaporator to give a residue that was purified by silica gel column chromatography eluted with DCM/MeOH (50:1) affording 3-((3-(1H-pyrazol-5-yl)piperidin-1-yl)methyl)-9-ethyl-9H-carbazole as a white solid (0.211 g, 5%). LCMS: [M+H]+: 359.2. 1H NMR (CDCl3,300 MHz) δ 8.11 (m, 1H), 8.00 (s, 1H), 7.48-7.36 (m, 5H), 7.24 (m, 1H), 6.03 (s, 1H), 4.37 (m, 2H), 3.93 (br, 2H), 3.76 (s, 2H), 3.15-2.60 (m, 5H), 1.67-1.56 (m, 4H), 1.43 (t, 3H).

Workup

  1. stirringto stir at room temperature overnight
  2. customUpon completion, the reaction was quenched by the addition of saturated aqueous Na2CO3 (150 mL)
  3. extractionThe resulting mixture was extracted with ethyl acetate (5×200 mL)
  4. dry with materialCombined organic layers were dried over MgSO4
  5. filtrationfiltered off
  6. concentrationconcentrated on a rotary evaporator
  7. customto give a residue that
  8. customwas purified by silica gel column chromatography
  9. washeluted with DCM/MeOH (50:1)

Sources & evidence

ORD record
ord-d0a40256e92140fb9a356210220d13c4
Source dataset
uspto-grants-2011_12
Patent number
US08080566B1

Reaction notes

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