Triethylamine → HCID 11697537, compound

HRID 969861Notes

Reaction equation

HRID 969861 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.[ClH:22].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]=[C:16]([Cl:22])[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 11697537HCID 11697537, compoundYield 32%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of 2-(2-(dimethylamino)phenyl)benzo[d]oxazole-4-carboxylic acid (100 mg, 0.32 mmol), (S)-(−)-3-aminoquinuclidine dihydrochloride (64 mg, 0.32 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (123 mg, 0.64 mmol) and 1-hydroxybenzotriazole (86 mg, 0.64 mmol) in DMF (1.5 mL) was stirred for 5 min at room temperature, then triethylamine (0.17 mL, 1.28 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 the (S)-N-(1-azabicyclo[2.2.2]oct-3-yl)-6-chloro-2-(2-dimethylaminophenyl)benzoxazole-4-carboxamide (43 mg, 32%) as a yellow solid: 1H NMR (500 MHz, CDCl3) δ 9.47 (d, J=7.5 Hz, 1H), 8.17 (d, J=2.0 Hz, 1H), 7.97 (dd, J=8.0, 1.5 Hz, 1H), 7.71 (d, J=2.0 Hz, 1H), 7.50-7.45 (m, 1H), 7.13 (d, J=8.5 Hz, 1H), 7.02 (t, J=8.0 Hz, 1H), 4.28-4.25 (m, 1H), 3.49 (ddd, J=11.5, 9.5, 2.0 Hz, 1H), 3.08-2.84 (m, 4H), 2.84 (s, 6H), 2.76 (dd, J=14.0, 4.5 Hz, 1H), 2.13-2.10 (m, 1H), 1.99-1.94 (m, 1H), 1.76-1.68 (m, 2H), 1.58-1.52 (m, 1H); MS (ESI+) m/z 425 (M+H); HPLC>99% (AUC), tR=13.47 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-34eec07d308a448090d3e1eb54fd587d
Source dataset
uspto-grants-2007_12
Patent number
US07307094B2

Reaction notes

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