Triethylamine → HCID 68455429, compound

HRID 506319Notes

Reaction equation

HRID 506319 reaction equation
[Cl:1][C:2]1[S:6][C:5]([C:7]2[O:8][C:9]3[C:10](=[C:12]([C:16]([OH:18])=O)[CH:13]=[CH:14][CH:15]=3)[N:11]=2)=[CH:4][CH:3]=1.Cl.C(N=C=NCCCN(C)C)C.ON1C2C=CC=CC=2N=N1.Cl.Cl.[NH2:43][C@H:44]1[CH:49]2[CH2:50][CH2:51][N:46]([CH2:47][CH2:48]2)[CH2:45]1.C(N(CC)CC)C>CN(C=O)C.ClCCl>[N:46]12[CH2:51][CH2:50][CH:49]([CH2:48][CH2:47]1)[C@H:44]([NH:43][C:16]([C:12]1[CH:13]=[CH:14][CH:15]=[C:9]3[O:8][C:7]([C:5]4[S:6][C:2]([Cl:1])=[CH:3][CH:4]=4)=[N:11][C:10]=13)=[O:18])[CH2:45]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 68458604HCID 68458604, compound

Product 1

HCID 68455429HCID 68455429, compoundYield 17%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of 2-(5-chlorothiophen-2-yl)benzoxazole-4-carboxylic acid (110 mg, 0.39 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (149 mg, 0.78 mmol), 1-hydroxybenzotriazole (106 mg, 0.78 mmol) and (S)-(−)-3-aminoquinuclidine dihydrochloride (135 mg, 0.49 mmol) in DMF (3 mL) was stirred at room temperature for 10 min, then triethylamine (0.22 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 (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-(5-chloro-thiophen-2-yl)benzoxazole-4-carboxamide (22 mg, 17%) as a white solid: 1H NMR (500 MHz, CDCl3) δ 9.41 (d, J=7.3 Hz, 1H), 8.17 (dd, J=7.8, 1.0 Hz, 1H), 7.73 (d, J=4.1 Hz, 1H), 7.69 (dd, J=8.2, 1.0 Hz, 1H), 7.48 (t, J=8.0 Hz, 1H), 7.06 (d, J=4.0 Hz, 1H), 4.50-4.45 (m, 1H), 3.65-3.60 (m, 1H), 3.30-3.20 (m, 2H), 3.15-3.05 (m, 2H), 3.02-2.95 (m, 1H), 2.30-2.55 (m, 2H), 1.95-1.78 (m, 3H); MS (ESI+) m/z 388 (M+H); HPLC>99% (AUC), tR=12.59 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 (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-c4bdfb7043dd48878b7bc6afb9116648
Source dataset
uspto-grants-2010_08
Patent number
US07781430B2

Reaction notes

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