Triethylamine → 1,3-Benzoxazole-4-carboxamide

HRID 506306Notes

Reaction equation

HRID 506306 reaction equation
F[C:2]1[CH:3]=[C:4]2[O:8][C:7](C3C=CC=CC=3)=[N:6][C:5]2=[C:15]([C:17]([OH:19])=O)[CH:16]=1.Cl.Cl.[NH2:22]C1CC2N(C)C(CCC2)C1.Cl.C(N=C=NCCCN(C)C)C.ON1C2C=CC=CC=2N=N1.C(N(CC)CC)C>CN(C=O)C>[O:8]1[C:4]2=[CH:3][CH:2]=[CH:16][C:15]([C:17]([NH2:22])=[O:19])=[C:5]2[N:6]=[CH:7]1

Participants

7

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 684583556-Fluoro-2-phenylbenzo[d]oxazole-4-carboxylic acid

Product 1

HCID 183694961,3-Benzoxazole-4-carboxamideYield 215.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 6-fluoro-2-phenylbenzo[d]oxazole-4-carboxylic acid (30 mg, 0.12 mmol), 3-amino-9-methyl-9-azabicyclo[3.3.1]nonane dihydrochloride (32 mg, 0.14 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (46 mg, 0.24 mmol) and 1-hydroxybenzotriazole (32 mg, 0.24 mmol) in DMF (5 mL) was stirred under nitrogen at room temperature for 10 min, and then triethylamine (0.10 mL, 0.72 mmol) was added. The resulting reaction mixture was stirred at room temperature overnight, and then was quenched with a saturated solution of sodium bicarbonate, extracted with methylene chloride. The combined organic layers were washed with brine, 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-fluoro-2-phenyl)benzoxazole-4-carboxamide (42 mg, 91%) as a light yellow solid: 1H NMR (500 MHz, CDCl3) δ 8.96 (d, J=7.5 Hz, 1H), 8.23-8.22 (m, 2H), 7.96 (d, J=10.5 Hz, 1H), 7.63-7.55 (m, 3H), 7.42 (d, J=7.0 Hz, 1H), 4.62-4.53 (m, 1H), 3.13-3.11 (m, 2H), 2.67-2.60 (m, 2H), 2.54 (s, 3H), 2.15-1.98 (m, 3H), 1.62-1.46 (m, 3H), 1.18-1.13 (m, 2H); 19F NMR (282 MHz, CDCl3) δ-113.93; MS (ESI+) m/z 394 (M+H); HPLC>99% (AUC), tR=12.78 min.

Workup

  1. customThe resulting reaction mixture
  2. stirringwas stirred at room temperature overnight
  3. customwas quenched with a saturated solution of sodium bicarbonate
  4. extractionextracted with methylene chloride
  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 column chromatography (silica gel, 90:9:1 ethyl acetate/methanol/concentrated ammonium hydroxide)

Sources & evidence

ORD record
ord-44c7479334d748c0927a26c92c3cb37e
Source dataset
uspto-grants-2010_08
Patent number
US07781430B2

Reaction notes

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