Triethylamine → HCID 11625837, compound

HRID 506283Notes

Reaction equation

HRID 506283 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=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.[NH2:23][C@H:24]1[CH:29]2[CH2:30][CH2:31][N:26]([CH2:27][CH2:28]2)[CH2:25]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:26]12[CH2:31][CH2:30][CH:29]([CH2:28][CH2:27]1)[C@H:24]([NH:23][C:18]([C:14]1[CH:15]=[CH:16][CH:17]=[C:11]3[O:10][C:9]([C:3]4[CH:4]=[CH:5][C:6]([Cl:8])=[CH:7][C:2]=4[Cl:1])=[N:13][C:12]=13)=[O:20])[CH2:25]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 68459328HCID 68459328, compound

Product 1

HCID 11625837HCID 11625837, compoundYield 47.3%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of 2-(2,4-dichlorophenyl)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 at room temperature for 5 min, 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 (S)—N-(1-azabicyclo[2.2.2]oct-3-yl)-2-(2,4-dichlorophenyl)benzoxazole-4-carboxamide (63 mg, 47%) as a white solid: 1H NMR (500 MHz, CDCl3) δ 9.40 (d, J=7.0 Hz, 1H), 8.25 (dd, J=7.5, 1.0 Hz, 1H), 8.17 (d, J=8.5 Hz, 1H), 7.75 (dd, J=8.0, 1.0 Hz, 1H), 7.65 (d, J=2.0 Hz, 1H), 7.54 (t, J=8.0 Hz, 1H), 7.47 (dd, J=8.5, 2.0 Hz, 1H), 4.32-4.26 (m, 1H), 3.50 (ddd, J=11.5, 9.5, 2.0 Hz, 1H), 3.10-2.72 (m, 5H), 2.15-2.10 (m, 1H), 2.02-1.95 (m, 1H), 1.82-1.70 (m, 2H), 1.60-1.51 (m, 1H); MS (ESI+) m/z 416 (M+H); HPLC>99% (AUC), tR=13.23 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-b8a1226b1d0145c3ae4639684c3c8cc6
Source dataset
uspto-grants-2010_08
Patent number
US07781430B2

Reaction notes

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