Triethylamine → (3R,4R)-2-(3,4-Dihydroxypyrrolidin-1-yl)-4-(3-fluorophenyl)-6-methoxyquinoline-3-carbonitrile

HRID 640727Notes

Reaction equation

Cl[C:2]1[C:11]([C:12]#[N:13])=[C:10]([C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([F:20])[CH:15]=2)[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([O:21][CH3:22])[CH:8]=2)[N:3]=1.[OH:23][C@H:24]1[C@H:28]([OH:29])[CH2:27][NH:26][CH2:25]1.C(N(CC)CC)C>CC(O)C.CCOC(C)=O>[OH:23][C@H:24]1[C@H:28]([OH:29])[CH2:27][N:26]([C:2]2[C:11]([C:12]#[N:13])=[C:10]([C:14]3[CH:19]=[CH:18][CH:17]=[C:16]([F:20])[CH:15]=3)[C:9]3[C:4](=[CH:5][CH:6]=[C:7]([O:21][CH3:22])[CH:8]=3)[N:3]=2)[CH2:25]1

Participants

Conditions

Temperature: 150 °C

Procedure

A solution of 2-chloro-4-(3-fluorophenyl)-6-methoxyquinoline-3-carbonitrile (61.0 mg, 0.20 mmol), (3R,4R)-3,4-dihydroxypyrrolidine (43 mg, 0.42 mmol) and triethylamine (0.055 mL, 0.42 mmol) in 3 mL of 2-propanol was heated in a sealed tube at 120° C. for 3 days. The temperature was raised to 150° C. After 3 days, additional portions of (3R,4R)-3,4-dihydroxypyrrolidine (40 mg) and triethylamine (0.055 mL) were added. After a total of 11 days, the solution was cooled and diluted with EtOAc. The organic layer was washed with saturated NaHCO3 solution and brine, and dried over Na2SO4, filtered, and concentrated in vacuo. The crude residue was purified by recrystallization from EtOAc/hexane (40 mg, 54%). Proton NMR for the product was consistent with the titled compound. HRMS (ES) exact mass calculated for C21H19FN3O3 (M+M+): 380.1405. Found 380.1401.

Workup

temperatureAfter a total of 11 days, the solution was cooled
washThe organic layer was washed with saturated NaHCO3 solution and brine
dry with materialdried over Na2SO4
filtrationfiltered
concentrationconcentrated in vacuo
customThe crude residue was purified by recrystallization from EtOAc/hexane (40 mg, 54%)

Sources & evidence

ORD record: ord-f19199f70c354cd69467086bdc40cb5d
Source dataset: uspto-grants-2010_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07692017B2

Reaction notes

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