Triethylamine → HCID 11718427, compound

HRID 506282Notes

Reaction equation

HRID 506282 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[C:7]([O:9][CH3:10])[CH:6]=[CH:5][C:4]=1[C:11]1[O:12][C:13]2[C:14](=[C:16]([C:20](O)=[O:21])[CH:17]=[CH:18][CH:19]=2)[N:15]=1.Cl.Cl.[NH2:25][C@H:26]1[CH:31]2[CH2:32][CH2:33][N:28]([CH2:29][CH2:30]2)[CH2:27]1.Cl.C(N=C=NCCCN(C)C)C.ON1C2C=CC=CC=2N=N1.C(N(CC)CC)C>CN(C=O)C.ClCCl>[N:28]12[CH2:33][CH2:32][CH:31]([CH2:30][CH2:29]1)[C@H:26]([NH:25][C:20]([C:16]1[CH:17]=[CH:18][CH:19]=[C:13]3[O:12][C:11]([C:4]4[CH:5]=[CH:6][C:7]([O:9][CH3:10])=[CH:8][C:3]=4[O:2][CH3:1])=[N:15][C:14]=13)=[O:21])[CH2:27]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 68459209HCID 68459209, compound

Product 1

HCID 11718427HCID 11718427, compoundYield 46%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of 2-(2,4-dimethoxyphenyl)benzo[d]oxazole-4-carboxylic acid (100 mg, 0.33 mmol), (S)-(−)-3-aminoquinuclidine dihydrochloride (66 mg, 0.33 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (126 mg, 0.66 mmol) and 1-hydroxybenzotriazole (89 mg, 0.66 mmol) in DMF (1.5 mL) was stirred at room temperature for 5 min, then triethylamine (0.18 mL, 1.32 mmol) was added. The resulting reaction mixture was stirred at room temperature for 12 h. The mixture was diluted with dichloromethane (20 mL), then washed with a saturated solution of sodium bicarbonate (10 mL). The aqueous layer was further extracted with dichloromethane (3×15 mL). The combined organics were dried (Na2SO4), filtered and concentrated. The crude material was purified by column chromatography (silica gel, 89:10:1 dichloromethane/methanol/concentrated ammonium hydroxide) to afford (S)—N-(1-azabicyclo[2.2.2]oct-3-yl)-2-(2,4-dimethoxyphenyl)benzoxazole-4-carboxamide (61 mg, 46%) as a white solid: 1H NMR (500 MHz, CDCl3) δ 9.68 (d, J=7.0 Hz, 1H), 8.16 (d, J=7.5 Hz, 1H), 8.11 (d, J=8.5 Hz, 1H), 7.68 (d, J=8.0 Hz, 1H), 7.41 (t, J=8.0 Hz, 1H), 6.68-6.65 (m, 2H), 4.32-4.26 (m, 1H), 4.00 (s, 3H), 3.92 (s, 3H), 3.50 (ddd, J=11.5, 9.5, 2.0 Hz, 1H), 3.10-2.86 (m, 4H), 2.83 (dd, J=14.5, 4.5 Hz, 1H), 2.22-2.17 (m, 1H), 2.10-1.98 (m, 1H), 1.78-1.70 (m, 2H), 1.60-1.51 (m, 1H); MS (ESI+) m/z 408 (M+H); HPLC 96.1% (AUC), tR=12.82 min.

Workup

  1. customThe resulting reaction mixture
  2. stirringwas stirred at room temperature for 12 h
  3. washwashed with a saturated solution of sodium bicarbonate (10 mL)
  4. extractionThe aqueous layer was further extracted with dichloromethane (3×15 mL)
  5. dry with materialThe combined organics were dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude material was purified by column chromatography (silica gel, 89:10:1 dichloromethane/methanol/concentrated ammonium hydroxide)

Sources & evidence

ORD record
ord-1207376eae7146ba838b3b6293eaa36d
Source dataset
uspto-grants-2010_08
Patent number
US07781430B2

Reaction notes

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