Water → HCID 66719106, compound

HRID 2390455Notes

Reaction equation

[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH2:11][CH2:12]Cl)[N:6]=[CH:5]2.Cl.[C@H:15]12[CH2:21][C@H:18]([NH:19][CH2:20]1)[CH2:17][O:16]2.C([O-])([O-])=O.[K+].[K+].O>CN(C=O)C>[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH2:11][CH2:12][N:19]1[CH2:20][C@@H:15]3[CH2:21][C@H:18]1[CH2:17][O:16]3)[N:6]=[CH:5]2

Participants

Conditions

Temperature: 90 °C

Procedure

5-Bromo-1-(2-chloroethyl)-1H-indazole (183 mg, 0.703 mmol) was added to a suspension of (1S,4S)-(+)-5-aza-2-oxabicyclo[2.2.1]heptane hydrochloride (286 mg, 2.11 mmol), K2CO3 (485 mg, 3.52 mmol) and KI (117 mg, 0.703 mmol) in DMF (10 mL) under N2. The resulting suspension was stirred at 90° C. for 19 h. The suspension was cooled, and H2O (10 mL) was added. The aqueous solution was extracted with EtOAc, and the combined organic extracts were washed with brine. The organic solution was dried over Na2SO4 and concentrated under reduced pressure to afford clear viscous oil. Flash chromatography on silica gel (100:0 to 0:100 hexanes/(9:0.9:0.1 CH2Cl2/MeOH/NH4OH)) gave the title compound (88 mg, 39%) as a clear oil: 1H NMR (300 MHz, CDCl3) δ 7.95-7.92 (m, 1H), 7.87-7.84 (m, 1H), 7.45 (dd, J=8.7, 1.8 Hz, 1H), 7.34 (d, J=8.7 Hz, 1H), 4.43 (t, J=6.7 Hz, 2H), 4.34 (br s, 1H), 3.92 (d, J=7.8 Hz, 1H), 3.56 (dd, J=7.8, 1.5 Hz, 1H), 3.34 (br s, 1H), 3.15-3.01 (m, 2H), 2.92 (d, J=21.9 Hz, 1H), 2.81 (dd, J=9.9, 1.5 Hz, 1H), 2.47 (br d, J=9.9 Hz, 1H), 1.79-1.60 (m, 1H).

Workup

temperatureThe suspension was cooled
extractionThe aqueous solution was extracted with EtOAc
washthe combined organic extracts were washed with brine
dry with materialThe organic solution was dried over Na2SO4
concentrationconcentrated under reduced pressure
customto afford clear viscous oil

Sources & evidence

ORD record: ord-1766bc074a044ae4b28f6451dc535be1
Source dataset: uspto-grants-2012_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08273770B2

Reaction notes

Loading…