Triethylamine → HCID 11619171, compound

HRID 506290Notes

Reaction equation

HRID 506290 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[C:9]1[O:10][C:11]2[C:12](=[C:14]([C:18](O)=[O:19])[CH:15]=[CH:16][CH:17]=2)[N:13]=1.Cl.Cl.[NH2:23][CH:24]1[CH2:31][CH:30]2[N:32]([CH3:33])[CH:26]([CH2:27][CH2:28][CH2:29]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>[CH3:33][N:32]1[CH:26]2[CH2:27][CH2:28][CH2:29][CH:30]1[CH2:31][CH:24]([NH:23][C:18]([C:14]1[CH:15]=[CH:16][CH:17]=[C:11]3[O:10][C:9]([C:3]4[C:4]([Cl:8])=[CH:5][CH:6]=[CH:7][C:2]=4[Cl:1])=[N:13][C:12]=13)=[O:19])[CH2:25]2

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 10881374HCID 10881374, compoundHCID 189569979-Methyl-9-azabicyclo[3.3.1]nonan-3-amine;dihydrochloride

Product 1

HCID 11619171HCID 11619171, compoundYield 38.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of 2-(2,6-dichlorophenyl)benzoxazole-4-carboxylic acid (71 mg, 0.23 mmol), 3-amino-9-methyl-9-azabicyclo[3.3.1]nonane dihydrochloride (64 mg, 0.28 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (88 mg, 0.46 mmol) and 1-hydroxybenzotriazole (62 mg, 0.46 mmol) in DMF (2 mL) was stirred at room temperature for 10 min, then triethylamine (0.16 mL, 1.16 mmol) was added. The resulting reaction mixture was stirred at room temperature overnight. The mixture was diluted with dichloromethane (30 mL), and then washed with a saturated solution of sodium bicarbonate (10 mL). The aqueous layer was further extracted with dichloromethane (2×30 mL). The combined organics were dried (Na2SO4), filtered and concentrated. The crude material was purified by column chromatography (silica gel, 90:9:1 ethyl acetate/methanol/concentrated ammonium hydroxide) and recrystallization from acetonitrile to afford N-(9-methyl-9-azabicyclo[3.3.1]non-3-yl)-2-(2,6-dichlorophenyl)benzoxazole-4-carboxamide (39 mg, 38%) as off-white crystals: 1H NMR (500 MHz, CDCl3) δ 8.85 (s, 1H), 8.29 (d, J=7.5 Hz, 1H), 7.76 (d, J=7.5 Hz, 1H), 7.57-7.46 (m, 4H), 4.62-4.54 (m, 1H), 3.14-3.06 (m, 2H), 2.53 (s, 3H), 2.05-1.92 (m, 3H), 1.65-1.40 (m, 5H), 1.16-1.05 (m, 2H); MS (ESI+) m/z 444 (M+H); HPLC>99% (AUC), tR=12.70 min.

Workup

  1. customThe resulting reaction mixture
  2. stirringwas stirred at room temperature overnight
  3. washwashed with a saturated solution of sodium bicarbonate (10 mL)
  4. extractionThe aqueous layer was further extracted with dichloromethane (2×30 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, 90:9:1 ethyl acetate/methanol/concentrated ammonium hydroxide) and recrystallization from acetonitrile

Sources & evidence

ORD record
ord-b68f7b70472b4c12acf39289899118b9
Source dataset
uspto-grants-2010_08
Patent number
US07781430B2

Reaction notes

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