Triethylamine → HCID 58088274, compound

HRID 250082

Reaction equation

HRID 250082 reaction equation
[N:1]([C:4]1[CH:11]=[C:10]([CH3:12])[C:7]([C:8]#[N:9])=[C:6]([CH3:13])[N:5]=1)=[C:2]=S.C(N(CC)CC)C.Cl.Cl.[NH2:23][CH2:24][C:25]1([OH:33])[CH:30]2[CH2:31][CH2:32][N:27]([CH2:28][CH2:29]2)[CH2:26]1.C(N=C=NC(C)C)(C)C>CN(C)C=O>[N:27]12[CH2:32][CH2:31][CH:30]([CH2:29][CH2:28]1)[C@@:25]1([O:33][C:2]([NH:1][C:4]3[CH:11]=[C:10]([CH3:12])[C:7]([C:8]#[N:9])=[C:6]([CH3:13])[N:5]=3)=[N:23][CH2:24]1)[CH2:26]2

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 12734DiisopropylcarbodiimideHCID 183162016-Isothiocyanato-2,4-dimethylnicotinonitrileHCID 198833963-(Aminomethyl)-1-azabicyclo(2.2.2)octan-3-ol dihydrochloride

Product 1

HCID 58088274HCID 58088274, compoundYield 66.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
70 °C

Procedure

To 6-isothiocyanato-2,4-dimethylnicotinonitrile (0.09 g, 0.48 mmol) in N,N-dimethylformamide (20 mL) was added triethylamine (0.17 mL, 1.19 mmol) and 3-(aminomethyl)quinuclidin-3-ol dihydrochloride (0.11 g, 0.49 mmol) at room temperature. The reaction was stirred at 70° C. for 2 hours. The reaction was cooled to room temperature and concentrated in vacuo. The crude urea was purified by chromatography (Biotage: 85% CHCl3, 14% MeOH, 1% NH4OH). The product was then treated with N,N-dimethylformamide (20 mL) and N,N′-diisopropylcarbodiimide (0.22 mL, 1.43 mmol). The reaction was heated to 70° C. for 2 hours. The reaction was cooled to room temperature and concentrated in vacuo to yield the crude product. The crude product was purified by chromatography (Biotage: 85% CHCl3, 14% MeOH, 1% NH4OH) to yield (R)-6-(4H-1′-azaspiro[oxazole-5,3′-bicyclo[2.2.2]octane]-2-ylamino)-2,4-dimethylnicotinonitrile (0.10 g, 0.32 mmol, 66% yield) as a white powder. 1H NMR (500 MHz, DMSO-D6) δ ppm 9.08 (s, 1 H), 6.60 (s, 1 H), 3.88 (d, J=10.38 Hz, 1 H), 3.61 (d, J=10.38 Hz, 1 H), 2.98 (s, 2 H), 2.70-2.79 (m, 2 H), 2.63-2.69 (m, 2 H), 2.55-2.60 (m, 4 H), 2.31-2.39 (m, 4 H), 1.99 (s, 1 H), 1.89 (s, 1 H), 1.54-1.62 (m, 2 H), 1.41-1.49 (m, 1 H). MS (LC/MS) R.T.=0.78; [M+H]+=312.1.

Workup

  1. temperatureThe reaction was cooled to room temperature
  2. concentrationconcentrated in vacuo
  3. customThe crude urea was purified by chromatography (Biotage: 85% CHCl3, 14% MeOH, 1% NH4OH)
  4. temperatureThe reaction was heated to 70° C. for 2 hours
  5. temperatureThe reaction was cooled to room temperature
  6. concentrationconcentrated in vacuo
  7. customto yield the crude product
  8. customThe crude product was purified by chromatography (Biotage: 85% CHCl3, 14% MeOH, 1% NH4OH)

Sources & evidence

ORD record
ord-6ad11b17d4164fdc96b3aaf652a7b5ed
Source dataset
uspto-grants-2011_01
Patent number
US07863291B2

Linked notes

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