1-Hydroxybenzotriazole → HCID 11632535, compound

HRID 506280Notes

Reaction equation

HRID 506280 reaction equation
[O:1]1[C:5]2[CH:6]=[CH:7][C:8]([C:10]3[O:11][C:12]4[C:13](=[C:15]([C:19]([OH:21])=O)[CH:16]=[CH:17][CH:18]=4)[N:14]=3)=[CH:9][C:4]=2[O:3][CH2:2]1.Cl.Cl.[NH2:24][C@H:25]1[CH:30]2[CH2:31][CH2:32][N:27]([CH2:28][CH2:29]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>[N:27]12[CH2:32][CH2:31][CH:30]([CH2:29][CH2:28]1)[C@H:25]([NH:24][C:19]([C:15]1[CH:16]=[CH:17][CH:18]=[C:12]3[O:11][C:10]([C:8]4[CH:7]=[CH:6][C:5]5[O:1][CH2:2][O:3][C:4]=5[CH:9]=4)=[N:14][C:13]=13)=[O:21])[CH2:26]2

Participants

8

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 12494973(3S)-1-azabicyclo[2.2.2]octan-3-amine dihydrochlorideHCID 68454470HCID 68454470, compound

Product 1

HCID 11632535HCID 11632535, compoundYield 43.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 2-benzo[1,3]dioxol-5-yl-benzoxazole-4-carboxylic acid (29 mg, 0.10 mmol), (S)-3-aminoquinuclidine dihydrochloride (24 mg, 0.12 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (38 mg, 0.20 mmol) and 1-hydroxybenzotriazole (27 mg, 0.20 mmol) in DMF (5 mL) was stirred for 10 min at room temperature, then DIPEA (66 μL, 0.40 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) to afford (S)—N-(1-azabicyclo[2.2.2]oct-3-yl)-2-benzo[1,3]dioxol-5-yl-benzoxazole-4-carboxamide (17 mg, 42%) as a white solid: 1H NMR (500 MHz, CDCl3) δ 9.54 (d, J=7.0 Hz, 1H), 8.17 (dd, J=7.5, 1.0 Hz, 1H), 7.82 (dd, J=8.0, 1.5 Hz, 1H), 7.68 (dd, J=8.0, 1.0 Hz, 1H), 7.64 (d, J=1.5 Hz, 1H), 7.44 (t, J=8.0 Hz, 1H), 6.98 (d, J=8.5 Hz, 1H), 6.11 (s, 2H), 4.33-4.29 (m, 1H), 3.56-3.48 (m, 1H), 3.13-2.99 (m, 2H), 2.95-2.88 (m, 2H), 2.85-2.79 (m, 1H), 2.18-2.13 (m, 1H), 1.80-1.59 (m, 4H); MS (ESI+) m/z 392 (M+H); HPLC 97.4% (AUC), tR=12.51 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)

Sources & evidence

ORD record
ord-61b4a38602424e5a9a8331ac6690d330
Source dataset
uspto-grants-2010_08
Patent number
US07781430B2

Reaction notes

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