Triethylamine → HCID 11553973, compound

HRID 969883Notes

Reaction equation

HRID 969883 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[O:8][C:7]([C:9]3[CH:14]=[CH:13][C:12]([CH3:15])=[CH:11][CH:10]=3)=[N:6][C:5]2=[C:16]([C:18](O)=[O:19])[CH:17]=1.Cl.C(N=C=NCCCN(C)C)C.ON1C2C=CC=CC=2N=N1.Cl.Cl.[NH2:45][CH:46]1[CH:51]2[CH2:52][CH2:53][N:48]([CH2:49][CH2:50]2)[CH2:47]1.C(N(CC)CC)C>CN(C=O)C.C(OCC)(=O)C>[N:48]12[CH2:53][CH2:52][CH:51]([CH2:50][CH2:49]1)[CH:46]([NH:45][C:18]([C:16]1[CH:17]=[C:2]([Br:1])[CH:3]=[C:4]3[O:8][C:7]([C:9]4[CH:14]=[CH:13][C:12]([CH3:15])=[CH:11][CH:10]=4)=[N:6][C:5]=13)=[O:19])[CH2:47]2

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 197853Quinuclidine, 3-amino-, dihydrochlorideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 68459376HCID 68459376, compound

Product 1

HCID 11553973HCID 11553973, compoundYield 54%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 6-bromo-2-p-tolylbenzoxazole-4-carboxylic acid (85 mg, 0.26 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (60 mg, 0.31 mmol), 1-hydroxybenzotriazole (60 mg, 0.31 mmol) and 3-aminoquinuclidine dihydrochloride (61 mg, 0.31 mmol) in DMF (5 mL) was stirred 10 min at room temperature, then triethylamine (0.12 mL, 1.02 mmol) was added. The resulting reaction mixture was stirred at room temperature overnight. The mixture was diluted with ethyl acetate (20 mL), and then washed with a saturated solution of sodium bicarbonate. The aqueous layer was further extracted with ethyl acetate (2×25 mL). The combined organic layers were dried (Na2SO4), filtered and concentrated under reduced pressure. The crude material was purified by column chromatography (silica gel, 90:9:1 ethyl acetate/methanol/concentrated ammonium hydroxide) to afford N-(1-azabicyclo[2.2.2]oct-3-yl)-6-bromo-2-p-tolylbenzoxazole-4-carboxamide (60 mg, 54%) as a white solid: 1H NMR (500 MHz, CDCl3) δ 9.48 (d, J=7.3 Hz, 1H), 8.30 (d, J=1.8 Hz, 1H), 8.10 (d, J=8.3 Hz, 2H), 7.85 (d, J=1.8 Hz, 1H), 7.37 (d, J=8.0 Hz, 2H), 4.35-4.25 (m, 1H), 3.60-3.45 (m, 1H), 3.15-3.00 (m, 2H), 2.95-2.82 (m, 2H),

Workup

  1. customThe resulting reaction mixture
  2. stirringwas stirred at room temperature overnight
  3. washwashed with a saturated solution of sodium bicarbonate
  4. extractionThe aqueous layer was further extracted with ethyl acetate (2×25 mL)
  5. dry with materialThe combined organic layers were dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe crude material was purified by column chromatography (silica gel, 90:9:1 ethyl acetate/methanol/concentrated ammonium hydroxide)

Sources & evidence

ORD record
ord-77372a98cc634a599687b05e4b102cbe
Source dataset
uspto-grants-2007_12
Patent number
US07307094B2

Reaction notes

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