Acetic Acid → HCID 178497598, compound

HRID 2369927Notes

Reaction equation

HRID 2369927 reaction equation
[N:1]12[CH2:8][CH2:7][C:4]([CH2:9][NH2:10])([CH2:5][CH2:6]1)[CH2:3][CH2:2]2.[CH:11]([C:13]1[C:21]2[C:20]([C:22]([O:24][CH3:25])=[O:23])=[CH:19][CH:18]=[CH:17][C:16]=2[NH:15][N:14]=1)=O.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>O1CCOCC1>[N:1]12[CH2:8][CH2:7][C:4]([CH2:9][NH:10][CH2:11][C:13]3[C:21]4[C:20]([C:22]([O:24][CH3:25])=[O:23])=[CH:19][CH:18]=[CH:17][C:16]=4[NH:15][N:14]=3)([CH2:5][CH2:6]1)[CH2:3][CH2:2]2

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 5049666Sodium triacetoxyborohydrideHCID 22056669Quinuclidin-4-ylmethanamineHCID 178497600HCID 178497600, compound

Product 1

HCID 178497598HCID 178497598, compoundYield 106.6%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Conditions

Temperature
60 °C

Procedure

To a stirred solution of quinuclidin-4-ylmethanamine (1.0 g, 7.14 mmol) in 1,4-dioxane (30 mL) was added methyl 3-formyl-1H-indazole-4-carboxylate (1.2 g, 6.0 mmol) in 1,4-dioxane (10 mL). Then glacial acetic acid (1% of total solvent used) was added and the reaction mixture was stirred at 60° C. for 2 h. It was cooled to room temperature and sodium triacetoxyborohydride (3.8 g, 17.9 mmol) was added. The reaction mixture was stirred at room temperature for 4 h). The solvent was removed under reduced pressure and the crude material was purified by column chromatography (silica gel, 70:27:3 dichloromethane/methanol/concentrated ammonium hydroxide) to give methyl 3-((quinuclidin-4-ylmethylamino)methyl)-1H-indazole-4-carboxylate as a brown oil (2.1 g, quantitative yield): 1H NMR (500 MHz, CD3OD) δ 7.87 (d, J=8.0 Hz, 1H), 7.81 (d, J=8.0 Hz, 1H), 7.49 (t, J=8.0 Hz, 1H), 4.38 (s, 2H), 3.99 (s, 3H), 3.27 (t, J=8.0 Hz, 6H), 2.68 (s, 2H), 1.78 (t, J=8.0 Hz, 6H); MS (ESI+) m/z 329 (M+H).

Workup

  1. temperatureIt was cooled to room temperature
  2. stirringThe reaction mixture was stirred at room temperature for 4 h)
  3. customThe solvent was removed under reduced pressure
  4. customthe crude material was purified by column chromatography (silica gel, 70:27:3 dichloromethane/methanol/concentrated ammonium hydroxide)

Sources & evidence

ORD record
ord-63a653d19acb44ba8f4a3fdc595b1b72
Source dataset
uspto-grants-2014_04
Patent number
US08710046B2

Reaction notes

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