(Bis(2-methoxyethyl)amino)sulfur trifluoride → N-(((2S,4S)-1-(biphenylcarbonyl)-4-fluoropyrrolidin-2-yl)methyl)quinoline-8-carboxamide

HRID 60787

Reaction equation

[C:1]1([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[C:2]([C:7]([N:9]2[CH2:13][C@H:12](O)[CH2:11][C@H:10]2[CH2:15][NH:16][C:17]([C:19]2[CH:20]=[CH:21][CH:22]=[C:23]3[C:28]=2[N:27]=[CH:26][CH:25]=[CH:24]3)=[O:18])=[O:8])=[CH:3][CH:4]=[CH:5][CH:6]=1.COCCN(S(F)(F)[F:45])CCOC>C(Cl)Cl>[C:1]1([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[C:2]([C:7]([N:9]2[CH2:13][C@@H:12]([F:45])[CH2:11][C@H:10]2[CH2:15][NH:16][C:17]([C:19]2[CH:20]=[CH:21][CH:22]=[C:23]3[C:28]=2[N:27]=[CH:26][CH:25]=[CH:24]3)=[O:18])=[O:8])=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

Conditions

Temperature: -78 °C

Procedure

A mixture of N-(((2S,4R)-1-(biphenylcarbonyl)-4-hydroxypyrrolidin-2-yl)methyl)quinoline-8-carboxamide (0.045 g, 0.10 mmol) in DCM was cooled to −78° C., added with bis(2-methoxyethyl)aminosulfur trifluoride (Aldrich) (41 μL, 0.22 mmol) dropwise. The resulting solution was stirred at −78° C. for 0.5 h, allowed to warm to rt gradually over 1.5 h and stirred at rt for 0.5 h, which was quenched by slow addition of MeOH and purified by preparative HPLC using acetonitrile and water (0.1% TFA) as eluent to provide N-(((2S,4S)-1-(biphenylcarbonyl)-4-fluoropyrrolidin-2-yl)methyl)quinoline-8-carboxamide as a white solid. MS (ESI) 454.14 (M+H).

Workup

temperatureto warm to rt gradually over 1.5 h
stirringstirred at rt for 0.5 h
customwhich was quenched by slow addition of MeOH
custompurified by preparative HPLC

Sources & evidence

ORD record: ord-70bdcca6c67e416c95b9e9b78f4f3bf0
Source dataset: uspto-grants-2016_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09440982B2

Linked notes

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