Methanesulfonyl chloride → HCID 51034450, compound

HRID 2068260Notes

Reaction equation

[CH3:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH3:8])[C:3]=1[N:9]1[C:13](=[O:14])[CH2:12][C@:11]([CH:18]([CH3:20])[CH3:19])([C:15](O)=[O:16])[CH2:10]1.CS(Cl)(=O)=O.C(N(C(C)C)CC)(C)C.[CH:35]1([C:38]2[CH:39]=[C:40]([NH2:48])[CH:41]=[C:42]([C:44]([F:47])([F:46])[F:45])[CH:43]=2)[CH2:37][CH2:36]1>C1COCC1>[CH:35]1([C:38]2[CH:39]=[C:40]([NH:48][C:15]([C@@:11]3([CH:18]([CH3:19])[CH3:20])[CH2:12][C:13](=[O:14])[N:9]([C:3]4[C:4]([CH3:8])=[CH:5][CH:6]=[CH:7][C:2]=4[CH3:1])[CH2:10]3)=[O:16])[CH:41]=[C:42]([C:44]([F:46])([F:47])[F:45])[CH:43]=2)[CH2:36][CH2:37]1

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of (R)-1-(2,6-dimethylphenyl)-3-isopropyl-5-oxopyrrolidine-3-carboxylic acid (32 mg, 0.12 mmol) and methanesulfonyl chloride (12 μL, 0.15 mmol) in THF (0.6 mL) at 0° C. was added diisopropylethylamine (0.060 mL, 0.35 mmol). The solution was stirred 15 min at 0° C., warmed to ambient temperature, and 3-cyclopropyl-5-(trifluoromethyl)benzenamine (47 mg, 0.23 mmol) was subsequently added and the solution was heated at 55° C. overnight. The following day, the reaction mixture was purified via preparative HPLC to afford the desired amide as a white solid. 1H NMR (400 MHZ, CDCl): δ 9.89 (s, 1H), 7.86 (s, 1H), 7.56 (s, 1H), 7.05-7.17 (m, 4H), 3.97 (d, J=10.4 Hz, 1H), 3.67 (d, J=10.4 Hz, 1H), 3.04 (d, J=17.2 Hz, 1H), 2.65 (d, J=17.2 Hz, 1H), 2.36 (septet, J=6.8 Hz, 1H), 2.16 (s, 3H), 1.99-2.08 (m, 1H), 1.99 (s, 3H), 1.00-1.06 (m, 2H), 0.96 (t, J=6.8 Hz, 6H), 0.70-0.75 (m, 2H). LC-MS Rt (retention time): 3.02 min; MS: (ES) m/z 459 (M+H+).

Workup

temperaturewarmed to ambient temperature
temperaturethe solution was heated at 55° C. overnight
customThe following day, the reaction mixture was purified via preparative HPLC

Sources & evidence

ORD record: ord-00545858cb7245989576595cb199949f
Source dataset: uspto-grants-2012_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08293925B2

Reaction notes

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