Triethylamine → HCID 11682395, compound

HRID 969896Notes

Reaction equation

HRID 969896 reaction equation
[S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C:6]1[O:7][C:8]2[C:9](=[C:11]([C:15]([OH:17])=O)[CH:12]=[CH:13][CH:14]=2)[N:10]=1.Cl.Cl.[NH2:20][CH:21]1[CH2:28][CH:27]2[N:29]([CH3:30])[CH:23]([CH2:24][CH2:25][CH2:26]2)[CH2:22]1.Cl.C(N=C=NCCCN(C)C)C.ON1C2C=CC=CC=2N=N1.C(N(CC)CC)C>CN(C=O)C.C(OCC)(=O)C>[CH3:30][N:29]1[CH:23]2[CH2:24][CH2:25][CH2:26][CH:27]1[CH2:28][CH:21]([NH:20][C:15]([C:11]1[CH:12]=[CH:13][CH:14]=[C:8]3[O:7][C:6]([C:2]4[S:1][CH:5]=[CH:4][CH:3]=4)=[N:10][C:9]=13)=[O:17])[CH2:22]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 68458344HCID 68458344, compound

Product 1

HCID 11682395HCID 11682395, compoundYield 56%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 2-thiophen-2-ylbenzoxazole-4-carboxylic acid (64 mg, 0.26 mmol), 3-amino-9-methyl-9-azabicyclo[3.3.1]nonane dihydrochloride (70 mg, 0.37 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (99 mg, 0.52 mmol) and 1-hydroxybenzotriazole (99 mg, 0.74 mmol) in DMF (5 mL) was stirred for 10 min at room temperature, then triethylamine (0.17 mL, 1.3 mmol) was added. The resulting reaction mixture was stirred at room temperature overnight. The mixture was diluted with ethyl acetate (20 mL), and then washed with a saturated solution of sodium bicarbonate. The aqueous layer was further extracted with ethyl acetate (2×50 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 then recrystallized from acetonitrile to afford N-(9-methyl-9-azabicyclo[3.3.1]non-3-yl)-2-thiophen-2-ylbenzoxazole-4-carboxamide (55 mg, 56%) as an off-white solid: 1H NMR (500 MHz, CDCl3) δ 8.99 (d, J=7.0 Hz, 1H), 8.20 (dd, J=7.5, 0.5 Hz, 1H), 7.95 (dd, J=4.0, 1.0 Hz, 1H), 7.67-7.63 (m, 2H), 7.45 (t, J=4.0 Hz, 1H), 7.27-7.23 (m, 1H), 4.62-4.56 (m, 1H), 3.15-3.09 (m, 2H), 2.67-2.59 (m, 2H) 2.54 (s, 3H), 2.18-1.88 (m, 3H), 1.65-1.57 (m, 5H); MS (ESI+) m/z 382 (M+H); HPLC>99% (AUC), tR=24.24 min.

Workup

  1. customThe resulting reaction mixture
  2. stirringwas stirred at room temperature overnight
  3. washwashed with a saturated solution of sodium bicarbonate
  4. extractionThe aqueous layer was further extracted with ethyl acetate (2×50 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)
  9. customrecrystallized from acetonitrile

Sources & evidence

ORD record
ord-a557d78abb8949078de0510e6c9020a4
Source dataset
uspto-grants-2007_12
Patent number
US07307094B2

Reaction notes

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