Triethylamine → HCID 59017518, compound

HRID 506293Notes

Reaction equation

HRID 506293 reaction equation
[Cl: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]([Cl: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 68455393HCID 68455393, compound

Product 1

HCID 59017518HCID 59017518, compoundYield 18%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 6-chloro-2-(4-methoxyphenyl)benzoxazole carboxylic acid (42 mg, 0.14 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (60 mg, 0.31 mmol), 1-hydroxybenzotriazole (43 mg, 0.31 mmol) and 3-amino-9-methyl-9-azabicyclo[3.3.1]nonane dihydrochloride (43 mg, 0.19 mmol) in DMF (4 mL) was stirred for 10 min at room temperature, then triethylamine (0.08 mL, 0.55 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 (2×50 mL). The combined organic layers were washed with brine, dried (Na2SO4), filtered and concentrated. The crude material was purified by preparative TLC (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-chloro-2-(4-methoxyphenyl)benzoxazole-4-carboxamide (11 mg, 18%) as a white solid: 1H NMR (500 MHz, CDCl3) δ 8.98 (br s, 1H), 8.20-8.15 (m, 3H), 7.66 (d, J=1.8 Hz, 1H), 7.08 (d, J=8.7 Hz, 2H), 4.60-4.45 (m, 1H), 3.93 (s, 3H), 3.35-3.05 (m, 2H), 2.70-2.50 (m, 6H), 2.20-1.90 (m, 3H), 1.70-1.45 (m, 3H), 1.35-1.10 (m, 1H); MS (ESI+) m/z 440 (M+H); HPLC 97.8% (AUC), tR=13.65 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 (2×50 mL)
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude material was purified by preparative TLC (silica gel, 90:9:1 ethyl acetate/methanol/concentrated ammonium hydroxide)

Sources & evidence

ORD record
ord-701006fcec4f4468b43f1822ad27deeb
Source dataset
uspto-grants-2010_08
Patent number
US07781430B2

Reaction notes

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