Acetic Acid → HCID 178462454, compound

HRID 659635Notes

Reaction equation

HRID 659635 reaction equation
Cl.[N:2]1[CH:6]=[C:5]([CH:7]2[CH2:12][CH2:11][CH2:10][NH:9][CH2:8]2)[NH:4][N:3]=1.[CH2:13]([N:15]1[C:27]2[CH:26]=[CH:25][C:24]([CH:28]=O)=[CH:23][C:22]=2[C:21]2[C:16]1=[CH:17][CH:18]=[CH:19][CH:20]=2)[CH3:14].C(N(C(C)C)C(C)C)C.C(O)(=O)C.[BH3-]C#N.[Na+].C(=O)(O)[O-].[Na+].O>C(O)C.CO.C(Cl)Cl>[N:2]1[CH:6]=[C:5]([CH:7]2[CH2:12][CH2:11][CH2:10][N:9]([CH2:28][C:24]3[CH:25]=[CH:26][C:27]4[N:15]([CH2:13][CH3:14])[C:16]5[C:21]([C:22]=4[CH:23]=3)=[CH:20][CH:19]=[CH:18][CH:17]=5)[CH2:8]2)[NH:4][N:3]=1

Participants

10

Reactant 6

HCID 176Acetic AcidHCID 81531DiisopropylethylamineHCID 820559-ethyl-9H-carbazole-3-carbaldehydeHCID 5003444Sodium cyanoborohydrideHCID 86585896Sodium bicarbonate waterHCID 178478427HCID 178478427, compound

Product 1

HCID 178462454HCID 178462454, compoundYield 42.3%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
40 °C

Procedure

A 100-mL round-bottomed flask was charged with a solution of 3-(3H-1,2,3-triazol-4-yl)piperidine hydrochloride (500 mg, 3.29 mmol, 1.00 equiv) in ethanol (50 mL), 9-ethyl-9H-carbazole-3-carbaldehyde (890 mg, 3.99 mmol, 1.50 equiv), N-ethyl-N-isopropylpropan-2-amine (1.37 g, 10.62 mmol, 4.00 equiv), acetic acid (640 mg, 10.67 mmol, 4.00 equiv) and NaBH3CN (510 mg, 8.10 mmol, 3.00 equiv). The resulting solution was heated to 40° C. in an oil bath for 16 hours. The reaction progress was monitored by TLC (DCM: MeOH=10:1). Upon completion, pH was adjusted to 8 with sodium bicarbonate/water. The resulting mixture was then extracted with dichloromethane (4×80 mL). Combined organic layers were dried over anhydrous sodium sulfate, filtered off and concentrated on a rotary evaporator. The residue was purified by a silica gel column chromatography eluted with dichloromethane/methanol (40/1) affording 3-((3-(3H-1,2,3-triazol-4-yl)piperidin-1-yl)methyl)-9-ethyl-9H-carbazole as white solid (0.5 g, 42%). LCMS: [M+H]+: 360. 1H NMR (CDCl3, 300 MHz) δ 8.08 (d, 1H), 8.03 (s, 1H), 7.47 (m, 3H), 7.26 (m, 2H), 4.35 (d, 2H), 3.80 (m, 2H), 3.30 (s, 1H), 2.99 (s, 2H), 2.80 (s, 1H), 2.61 (s, 2H), 1.94 (s, 1H), 1.73 (s, 2H), 1.54 (s, 1H), 1.42 (t, 3H).

Workup

  1. extractionThe resulting mixture was then extracted with dichloromethane (4×80 mL)
  2. dry with materialCombined organic layers were dried over anhydrous sodium sulfate
  3. filtrationfiltered off
  4. concentrationconcentrated on a rotary evaporator
  5. customThe residue was purified by a silica gel column chromatography
  6. washeluted with dichloromethane/methanol (40/1)

Sources & evidence

ORD record
ord-2597c823dbd3402986c11a613688ab5f
Source dataset
uspto-grants-2011_12
Patent number
US08080566B1

Reaction notes

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