1,8-Diazabicyclo(5.4.0)undec-7-ene → 2,5-Difluoro-4-(3-hydroxyazetidin-1-yl)-N-[(1S)-2,2,2-trifluoro-1-methylethyl]benzamide

HRID 1049138Notes

Reaction equation

[F:1][C:2]1[CH:16]=[C:15](F)[C:14]([F:18])=[CH:13][C:3]=1[C:4]([NH:6][C@@H:7]([CH3:12])[C:8]([F:11])([F:10])[F:9])=[O:5].Cl.[NH:20]1[CH2:23][CH:22]([OH:24])[CH2:21]1.N12CCCN=C1CCCCC2>C(#N)C.CCOC(C)=O>[F:1][C:2]1[CH:16]=[C:15]([N:20]2[CH2:23][CH:22]([OH:24])[CH2:21]2)[C:14]([F:18])=[CH:13][C:3]=1[C:4]([NH:6][C@@H:7]([CH3:12])[C:8]([F:11])([F:10])[F:9])=[O:5]

Participants

Conditions

Temperature: 80 °C

Procedure

A mixture of 2,4,5-trifluoro-N-[(1S)-2,2,2-trifluoro-1-methylethyl]benzamide (6.39 g, 23.6 mmol), azetidin-3-ol hydrochloride (3.19 g, 28.3 mmol) and 1,8-diazabicyclo[5.4.0]undec-7-ene (8.81 mL, 58.9 mmol) in acetonitrile (25 mL) was stirred at 80° C. for 2 h. The reaction mixture was diluted with EtOAc (75 mL) and washed with 1N HCl (50 mL), 1N NaHCO3 (60 mL), 20% brine (50 mL) and water (75 mL). The aqueous layers were extracted with EtOAc (100 mL). The organic layers were combined, dried over MgSO4, filtered and concentrated under reduced pressure to yield the desired product (7.59 g, 91.8%). 1H NMR (300 MHz, DMSO-d6) δ 8.38 (dd, J=8.9, 1.9 Hz, 1H), 7.27 (dd, J=12.8, 6.5 Hz, 1H), 6.38 (dd, J=12.3, 7.5 Hz, 1H), 5.71 (d, J=6.4 Hz, 1H), 4.74 (dp, J=15.3, 7.6 Hz, 1H), 4.62-4.46 (m, 1H), 4.30-4.15 (m, 2H), 3.71 (m, 2H), 1.29 (d, J=7.1 Hz, 3H) ppm. LCMS cacld. for C13H14F5N2O2 (M+1)+: m/z=325.1. Found: 325.1.

Workup

washwashed with 1N HCl (50 mL), 1N NaHCO3 (60 mL), 20% brine (50 mL) and water (75 mL)
extractionThe aqueous layers were extracted with EtOAc (100 mL)
dry with materialdried over MgSO4
filtrationfiltered
concentrationconcentrated under reduced pressure

Sources & evidence

ORD record: ord-6a4d5465ca5948d0a6fb145bf40f7b17
Source dataset: uspto-grants-2016_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09382231B2

Reaction notes

Loading…