1-Hydroxybenzotriazole → HCID 11690256, compound

HRID 969859Notes

Reaction equation

HRID 969859 reaction equation
[CH3:1][N:2]([CH3:21])[C:3]1[CH:8]=[CH:7][C:6]([C:9]2[O:10][C:11]3[C:12](=[C:14]([C:18](O)=[O:19])[CH:15]=[CH:16][CH:17]=3)[N:13]=2)=[CH:5][CH:4]=1.Cl.Cl.[NH2:24][CH:25]1[CH2:32][CH:31]2[N:33]([CH3:34])[CH:27]([CH2:28][CH2:29][CH2:30]2)[CH2:26]1.Cl.C(N=C=NCCCN(C)C)C.ON1C2C=CC=CC=2N=N1.CCN(C(C)C)C(C)C>CN(C=O)C.C(OCC)(=O)C>[CH3:34][N:33]1[CH:27]2[CH2:28][CH2:29][CH2:30][CH:31]1[CH2:32][CH:25]([NH:24][C:18]([C:14]1[CH:15]=[CH:16][CH:17]=[C:11]3[O:10][C:9]([C:6]4[CH:5]=[CH:4][C:3]([N:2]([CH3:21])[CH3:1])=[CH:8][CH:7]=4)=[N:13][C:12]=13)=[O:19])[CH2:26]2

Participants

8

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 189569979-Methyl-9-azabicyclo[3.3.1]nonan-3-amine;dihydrochlorideHCID 68455765HCID 68455765, compound

Product 1

HCID 11690256HCID 11690256, compoundYield 41%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 2-(4-dimethylaminophenyl)benzoxazole-4-carboxylic acid (78 mg, 0.32 mmol), 3-amino-9-methyl-9-azabicyclo[3.3.1]nonane dihydrochloride (86 mg, 0.38 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (86 mg, 0.45 mmol) and 1-hydroxybenzotriazole (122 mg, 0.90 mmol) in DMF (5 mL) was stirred for 10 min at room temperature, then DIPEA (0.26 mL, 1.6 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 recrystallized from acetonitrile to afford N-(9-methyl-9-azabicyclo[3.3.1]non-3-yl)-2-(4-dimethylaminophenyl)benzoxazole-4-carboxamide (51 mg, 41%) as a yellow solid: 1H NMR (500 MHz, CDCl3) δ 9.21 (d, J=7.0 Hz, 1H), 8.15-8.09 (m, 3H), 7.61 (d, J=8.0 Hz, 1H), 7.35 (t, J=8.0 Hz, 1H), 6.80 (d, J=9.0 Hz, 2H), 4.61-4.54 (m, 1H), 3.10-3.15 (m, 8H), 2.68-2.62 (m, 2H), 2.55 (s, 3H), 2.05-1.96 (m, 2H), 1.59-1.49 (m, 4H), 1.22-1.19 (m, 1H); MS (ESI+) m/z 419 (M+H); HPLC 93.1% (AUC), tR=16.55 mm.

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-de2176fca8b94b23b66522ccd945b758
Source dataset
uspto-grants-2007_12
Patent number
US07307094B2

Reaction notes

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