Triethylamine → HCID 11661096, compound

HRID 506272Notes

Reaction equation

HRID 506272 reaction equation
[CH3:1][N:2]([CH3:21])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]1[O:10][C:11]2[C:12](=[C:14]([C:18]([OH:20])=O)[CH:15]=[CH:16][CH:17]=2)[N:13]=1.Cl.Cl.[NH2:24][C@H:25]1[CH:30]2[CH2:31][CH2:32][N:27]([CH2:28][CH2:29]2)[CH2:26]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:27]12[CH2:32][CH2:31][CH:30]([CH2:29][CH2:28]1)[C@H:25]([NH:24][C:18]([C:14]1[CH:15]=[CH:16][CH:17]=[C:11]3[O:10][C:9]([C:4]4[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=4[N:2]([CH3:1])[CH3:21])=[N:13][C:12]=13)=[O:20])[CH2:26]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 68455828HCID 68455828, compound

Product 1

HCID 11661096HCID 11661096, compoundYield 34%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of 2-(2-(dimethylamino)phenyl)benzo[d]oxazole-4-carboxylic acid (100 mg, 0.35 mmol), (S)-(−)-3-aminoquinuclidine dihydrochloride (70 mg, 0.35 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (134 mg, 0.70 mmol) and 1-hydroxybenzotriazole (95 mg, 0.70 mmol) in DMF (1 mL) was stirred for 5 min at room temperature, then triethylamine (0.19 mL, 1.4 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-dimethylaminophenyl)benzoxazole-4-carboxamide (46 mg, 34%) as a yellow solid: 1H NMR (500 MHz, CDCl3) δ 9.60 (d, J=7.0 Hz, 1H), 8.19 (dd, J=7.5, 1.0 Hz, 1H), 7.99 (dd, J=8.0, 2.0 Hz, 1H), 7.71 (dd, J=8.0, 1.0 Hz, 1H), 7.49-7.42 (m, 2H), 7.13 (d, J=8.5 Hz, 1H), 7.03 (t, J=8.5 Hz, 1H), 4.28-4.26 (m, 1H), 3.49 (ddd, J=11.5, 9.5, 2.0 Hz, 1H), 3.10-2.85 (m, 4H), 2.85 (s, 6H), 2.77 (dd, J=14.0, 4.5 Hz, 1H), 2.15-2.11 (m, 1H), 2.04-1.98 (m, 1H), 1.78-1.70 (m, 2H), 1.60-1.51 (m, 1H); MS (ESI+) m/z 391 (M+H); HPLC>99% (AUC), tR=12.81 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-c44c8925c5d74ef483cf0f50e9196057
Source dataset
uspto-grants-2010_08
Patent number
US07781430B2

Reaction notes

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