Triethylamine → HCID 11603972, compound

HRID 969872Notes

Reaction equation

HRID 969872 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:9][C:10]3[C:11](=[C:13]([C:17](O)=[O:18])[CH:14]=[CH:15][CH:16]=3)[N:12]=2)=[C:4]([O:20][CH3:21])[CH:3]=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:17]([C:13]1[CH:14]=[CH:15][CH:16]=[C:10]3[O:9][C:8]([C:5]4[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][C:4]=4[O:20][CH3:21])=[N:12][C:11]=13)=[O:18])[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 68456721HCID 68456721, compound

Product 1

HCID 11603972HCID 11603972, compoundYield 54%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of 2-(4-chloro-2-methoxyphenyl)benzoxazole-4-carboxylic acid (95 mg, 0.31 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (119 mg, 0.62 mmol), 1-hydroxybenzotriazole (76 mg, 0.62 mmol) and (S)-(−)-3-aminoquinuclidine dihydrochloride (78 mg, 0.39 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 dichloromethane/methanol/concentrated ammonium hydroxide) to afford (S)-N-(1-azabicyclo[2.2.2]oct-3-yl)-2-(4-chloro-2-methoxyphenyl)benzoxazole-4-carboxamide (69 mg, 54%) as a white solid: 1H NMR (500 MHz, CDCl3) δ 9.59 (d, J=7.0 Hz, 1H), 8.19 (dd, J=7.8, 1.0 Hz, 1H), 8.08 (d, J=8.2 Hz, 1H), 7.83 (dd, J=8.2, 1.0 Hz, 1H), 7.47 (t, J=7.9 Hz, 1H), 7.15-7.10 (m, 2H), 4.40-4.22 (m, 1H), 4.02 (s, 3H), 3.55-3.50 (m, 1H), 3.20-2.75 (m, 5H), 2.23-2.19 (m, 1H), 2.10-2.00 (m, 1H), 1.80-1.75 (m, 2H), 1.60-1.50 (m, 1H); MS (ESI+) m/z 412 (M+H); HPLC>99% (AUC), tR=13.78 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 dichloromethane/methanol/concentrated ammonium hydroxide)

Sources & evidence

ORD record
ord-ffb1639edd814809b98fd834d17bfb63
Source dataset
uspto-grants-2007_12
Patent number
US07307094B2

Reaction notes

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