Triethylamine → N-(9-Methyl-9-azabicyclo[3.3.1]non-3-yl)-2-(2-hydroxyphenyl)benzoxazole-4-carboxamide Hydrochloride

HRID 506266Notes

Reaction equation

HRID 506266 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[O:9][C:10]2[C:11](=[C:13]([C:17]([OH:19])=O)[CH:14]=[CH:15][CH:16]=2)[N:12]=1.[ClH:20].C(N=C=NCCCN(C)C)C.ON1C2C=CC=CC=2N=N1.Cl.Cl.[NH2:44][CH:45]1[CH2:52][CH:51]2[N:53]([CH3:54])[CH:47]([CH2:48][CH2:49][CH2:50]2)[CH2:46]1.C(N(CC)CC)C>CN(C=O)C.ClCCl>[ClH:20].[CH3:54][N:53]1[CH:47]2[CH2:48][CH2:49][CH2:50][CH:51]1[CH2:52][CH:45]([NH:44][C:17]([C:13]1[CH:14]=[CH:15][CH:16]=[C:10]3[O:9][C:8]([C:3]4[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=4[OH:1])=[N:12][C:11]=13)=[O:19])[CH2:46]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 135957253Caboxamycin

Product 1

HCID 136344233N-(9-Methyl-9-azabicyclo[3.3.1]non-3-yl)-2-(2-hydroxyphenyl)benzoxazole-4-carboxamide HydrochlorideYield 48%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of 2-(2-hydroxyphenyl)benzoxazole-4-carboxylic acid (96 mg, 0.37 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (143 mg, 0.75 mmol), 1-hydroxybenzotriazole (102 mg, 0.75 mmol) and 3-amino-9-methyl-9-azabicyclo[3.3.1]nonane dihydrochloride (85 mg, 0.37 mmol) in DMF (5 mL) was stirred at room temperature for 10 min. then triethylamine (0.15 mL, 1.12 mmol) was added. The resulting reaction mixture was stirred at room temperature overnight. The mixture was diluted with dichloromethane and then washed with a saturated solution of sodium bicarbonate. The aqueous layer was further extracted with dichloromethane (2×50 mL). The combined organic layers were washed with water (2×50 mL) and brine (2×50 mL), dried (Na2SO4), filtered and concentrated. The crude material was purified by column chromatography (silica gel, 90:9:1 dichloromethane/methanol/concentrated ammonium hydroxide) and recrystallization from acetonitrile to afford the desired product (70 mg, 48%) as a white solid: 1H NMR (500 MHz, CDCl3) δ 10.54 (s, 1H), 8.21 (dd, J=7.8, 1.1 Hz, 1H), 8.09 (dd, J=8.1, 1.6 Hz, 1H), 7.80-7.77 (m, 1H), 7.75 (dd, J=8.1, 0.9 Hz, 1H), 7.57-7.50 (m, 2H), 7.17 (dd, J=8.6, 0.6 Hz, 1H), 7.10-7.05 (m, 1H), 4.70-4.60 (m, 1H), 3.25-3.15 (m, 2H), 2.73-2.69 (m, 2H), 2.56 (s, 3H), 2.15-1.95 (m, 2H), 1.65-1.45 (m, 4H), 1.25-1.10 (m, 2H); MS (ESI+) m/z 392 (M+H).

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 dichloromethane (2×50 mL)
  5. washThe combined organic layers were washed with water (2×50 mL) and brine (2×50 mL)
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude material was purified by column chromatography (silica gel, 90:9:1 dichloromethane/methanol/concentrated ammonium hydroxide) and recrystallization from acetonitrile

Sources & evidence

ORD record
ord-3c877ac2cd29462f80a91b7a2c2b2111
Source dataset
uspto-grants-2010_08
Patent number
US07781430B2

Reaction notes

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