Triethylamine → HCID 11668284, compound

HRID 506286Notes

Reaction equation

HRID 506286 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[O:10][C:11]3[C:12](=[C:14]([C:18](O)=[O:19])[CH:15]=[CH:16][CH:17]=3)[N:13]=2)=[C:5]([CH3:21])[CH:4]=1.Cl.C(N=C=NCCCN(C)C)C.ON1C2C=CC=CC=2N=N1.Cl.Cl.[NH2:46][C@H:47]1[CH:52]2[CH2:53][CH2:54][N:49]([CH2:50][CH2:51]2)[CH2:48]1.C(N(CC)CC)C>CN(C=O)C.ClCCl>[N:49]12[CH2:54][CH2:53][CH:52]([CH2:51][CH2:50]1)[C@H:47]([NH:46][C:18]([C:14]1[CH:15]=[CH:16][CH:17]=[C:11]3[O:10][C:9]([C:6]4[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][C:5]=4[CH3:21])=[N:13][C:12]=13)=[O:19])[CH2:48]2

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 12494973(3S)-1-azabicyclo[2.2.2]octan-3-amine dihydrochlorideHCID 68455849HCID 68455849, compound

Product 1

HCID 11668284HCID 11668284, compoundYield 30%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of 2-(4-methoxy-2-methylphenyl)benzoxazole-4-carboxylic acid (100 mg, 0.35 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (134 mg, 0.70 mmol), 1-hydroxybenzotriazole (95 mg, 0.70 mmol) and (S)-(−)-3-aminoquinuclidine dihydrochloride (87 mg, 0.44 mmol) in DMF (3 mL) was stirred at room temperature for 10 min, then triethylamine (0.20 mL, 1.4 mmol) was added. The resulting reaction mixture was stirred at room temperature overnight. The mixture was diluted with dichloromethane and then washed with a saturated solution of sodium bicarbonate. The aqueous layer was further extracted with dichloromethane (2×50 mL). The combined organic layers were washed with brine (2×50 mL), dried (Na2SO4), filtered and concentrated. The crude material was purified by column chromatography (silica gel, 90:9:1 ethyl acetate/methanol/concentrated ammonium hydroxide) to afford (S)—N-(1-azabicyclo[2.2.2]oct-3-yl)-2-(4-methoxy-2-methylphenyl)benzoxazole-4-carboxamide (41 mg, 30%) as an off-white solid: 1H NMR (500 MHz, CDCl3) δ 9.46 (d, J=7.0 Hz, 1H), 8.20-8.15 (m, 2H), 7.72 (dd, J=7.1, 1.0 Hz, 1H), 7.45 (t, J=7.9 Hz, 1H), 6.95-6.90 (m, 2H), 4.51-4.42 (m, 1H), 3.91 (s, 3H), 3.70-3.63 (m, 1H), 3.22-3.00 (m, 4H), 2.98-2.90 (m, 1H), 2.86 (s, 3H), 2.35-2.30 (m, 1H), 2.20-2.10 (m, 1H), 2.00-1.95 (m, 2H), 1.75-1.70 (m, 1H); MS (ESI+) m/z 392 (M+H); HPLC 96.6% (AUC), tR=13.19 min.

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 dichloromethane (2×50 mL)
  5. washThe combined organic layers were washed with brine (2×50 mL)
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude material was purified by column chromatography (silica gel, 90:9:1 ethyl acetate/methanol/concentrated ammonium hydroxide)

Sources & evidence

ORD record
ord-7e05dc3d66734f6a901179be20019b6a
Source dataset
uspto-grants-2010_08
Patent number
US07781430B2

Reaction notes

Loading…