Triethylamine → HCID 11712784, compound

HRID 969885Notes

Reaction equation

HRID 969885 reaction equation
[Br:1][C:2]1[CH:21]=[CH:20][C:5]2[NH:6][C:7]([C:12]3[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][CH:13]=3)(C(O)=O)[O:8][C:4]=2[CH:3]=1.Cl.C(N=C=NC[CH2:29][CH2:30][N:31]([CH3:33])C)C.[OH:34]N1C2C=CC=CC=2N=N1.Cl.Cl.N[CH:47]1[CH2:54]C2N(C)C(CCC2)C1.[CH2:57]([N:59]([CH2:62][CH3:63])[CH2:60][CH3:61])C>CN(C=O)C.C(OCC)(=O)C>[CH3:57][N:59]1[CH:62]2[CH2:63][CH2:54][CH2:47][CH:60]1[CH2:61][CH:30]([NH:31][C:33]([C:20]1[CH:21]=[C:2]([Br:1])[CH:3]=[C:4]3[O:8][C:7]([C:12]4[CH:13]=[CH:14][C:15]([O:18][CH3:19])=[CH:16][CH:17]=4)=[N:6][C:5]=13)=[O:34])[CH2:29]2

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 189569979-Methyl-9-azabicyclo[3.3.1]nonan-3-amine;dihydrochlorideHCID 68454474HCID 68454474, compound

Product 1

HCID 11712784HCID 11712784, compoundYield 27%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 6-bromo-2-(4-methoxyphenyl)benzoxazole carboxylic acid (86 mg, 0.25 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (94 mg, 0.49 mmol), 1-hydroxybenzotriazole (67 mg, 0.49 mmol) and 3-amino-9-methyl-9-azabicyclo[3.3.1]nonane dihydrochloride (67 mg, 0.30 mmol) in DMF (5 mL) was stirred for 10 min at room temperature, then triethylamine (0.100 mL, 0.99 mmol) was added. The resulting reaction mixture was stirred at room temperature for 18 h. The mixture was diluted with ethyl acetate and then washed with a saturated solution of sodium bicarbonate. The aqueous layer was further extracted with ethyl acetate (2×100 mL). The combined organic layers were washed with brine (2×100 mL), dried (Na2SO4), filtered and concentrated. The crude material was purified by column chromatography (silica gel, 90:9:1 ethyl acetate/methanol/concentrated ammonium hydroxide) to afford N-(9-methyl-9-azabicyclo[3.3.1]non-3-yl)-6-bromo-2-(4-methoxyphenyl)benzoxazole-4-carboxamide (32 mg, 27%) as a white solid: 1H NMR (500 MHz, CDCl3) δ 8.99 (br s, 1H), 8.30 (d, J=1.8 Hz, 1H), 8.17 (d, J=8.8 Hz, 2H), 7.81 (d, J=1.8 Hz, 1H), 7.10-7.05 (m, 2H), 4.60-4.55 (m, 1H), 3.93 (s, 3H), 3.25-3.15 (m, 2H), 2.70-2.55 (m, 5H), 2.40-2.00 (m, 3H), 1.70-1.20 (m, 5H); MS (ESI+) m/z 484 (M+H); HPLC>99% (AUC), tR=15.30 min.

Workup

  1. customThe resulting reaction mixture
  2. stirringwas stirred at room temperature for 18 h
  3. washwashed with a saturated solution of sodium bicarbonate
  4. extractionThe aqueous layer was further extracted with ethyl acetate (2×100 mL)
  5. washThe combined organic layers were washed with brine (2×100 mL)
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude material was purified by column chromatography (silica gel, 90:9:1 ethyl acetate/methanol/concentrated ammonium hydroxide)

Sources & evidence

ORD record
ord-954d8db17b684cbd89bb1a7d2d5e5dee
Source dataset
uspto-grants-2007_12
Patent number
US07307094B2

Reaction notes

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