1,4-Diazabicyclo(3.2.2)nonane → 4-(5-Bromobenzoxazol-2-yl)-1,4-diazabicyclo[3.2.2]nonane

HRID 393531Notes

Reaction equation

[N:1]12[CH2:9][CH2:8][CH:5]([CH2:6][CH2:7]1)[NH:4][CH2:3][CH2:2]2.[Br:10][C:11]1[CH:12]=[CH:13][C:14]2[O:18][C:17](SC)=[N:16][C:15]=2[CH:21]=1>CC(O)C>[Br:10][C:11]1[CH:12]=[CH:13][C:14]2[O:18][C:17]([N:4]3[CH:5]4[CH2:8][CH2:9][N:1]([CH2:7][CH2:6]4)[CH2:2][CH2:3]3)=[N:16][C:15]=2[CH:21]=1

Participants

Conditions

Temperature: 90 °C

Procedure

1,4-Diazabicyclo[3.2.2]nonane (57%, 731 mg, 3.31 mmol) was added to a solution of 5-bromo-2-methylsulfanyl-benzooxazole (538 mg, 2.20 mmol) in iPrOH (4.4 mL). The mixture was placed in an oil bath at 90° C. and the solvent was evaporated. The mixture was allowed to stir neat at 90° C. for 18 h. Upon cooling to RT the mixture was purified by chromatography (Biotage, 25M) eluting with 4% MeOH in CHCl3 with 20 drops of NH4OH per liter of eluent to afford 392 mg (55%) of the title compound as an oil: 1H NMR (CDCl3, 400 MHz) δ 7.40 (t, 1H, J=1.2 Hz), 7.05 (d, 2H, J=1.2 Hz), 4.46-4.43 (m, 1H), 3.87 (t, 2H, J=5.8 Hz), 3.14-2.93 (m, 6H), 2.13-2.06 (m, 2H), 1.81-1.73 (m, 2H); 13C NMR (CDCl3, 100 MHz) δ 162.3, 148.0, 145.6, 122.9, 119.0, 116.8, 109.8, 57.2, 50.5, 46.5, 44.4, 27.0; MS (Cl) m/z 322.0 (M+1); HPLC retention time=3.36 min. The hydrochloride salt was prepared by diluting in ethyl acetate and adding a solution of 2.5 N HCl in ethyl acetate: mp>300° C.

Workup

customThe mixture was placed in an oil bath at 90° C.
customthe solvent was evaporated
temperatureUpon cooling to RT the mixture
customwas purified by chromatography (Biotage, 25M)
washeluting with 4% MeOH in CHCl3 with 20 drops of NH4OH per liter of eluent

Sources & evidence

ORD record: ord-a9b201a566af4145a76ec814cedc6d3b
Source dataset: uspto-grants-2004_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06809094B2

Reaction notes

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