Methanesulfonyl chloride → HCID 51034224, compound

HRID 2068262Notes

Reaction equation

HRID 2068262 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]([O:38][C:39]1[CH:40]=[C:41]([NH2:49])[CH:42]=[C:43]([C:45]([F:48])([F:47])[F:46])[CH:44]=1)([CH3:37])[CH3:36]>C1COCC1>[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]([CH3:19])[CH3:20])([C:15]([NH:49][C:41]2[CH:42]=[C:43]([C:45]([F:47])([F:48])[F:46])[CH:44]=[C:39]([O:38][CH:35]([CH3:37])[CH3:36])[CH:40]=2)=[O:16])[CH2:10]1

Participants

6

Reactant 4

HCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 582187703-Isopropoxy-5-(trifluoromethyl)anilineHCID 58218830HCID 58218830, compound

Product 1

HCID 51034224HCID 51034224, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of (R)-1-(2,6-dimethylphenyl)-3-isopropyl-5-oxopyrrolidine-3-carboxylic acid (25 mg, 0.091 mmol) and methanesulfonyl chloride (9 μL, 0.12 mmol) in THF (0.9 mL) at 0° C. was added diisopropylethylamine (0.047 mL, 0.27 mmol). The solution was stirred 15 min at 0° C., warmed to ambient temperature, and 3-isopropoxy-5-(trifluoromethyl)benzenamine (39 mg, 0.18 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 9.91 (s, 1H), 7.59 (s, 1H), 7.56 (s, 1H), 7.04-7.16 (m, 3H), 6.90-6.94 (m, 1H), 4.65 (septet, J=6.0 Hz, 1H), 3.97 (d, J=10.4 Hz, 1H), 3.66 (d, J=10.8 Hz, 1H), 3.04 (d, J=17.2 Hz, 1H), 2.66 (d, J=17.2 Hz, 1H), 2.36 (septet, J=6.8 Hz, 1H), 2.16 (s, 3H), 2.00 (s, 3H), 1.29 (d, J=6.0 Hz, 6H), 0.96 (t, J=6.4 Hz, 6H). LC-MS Rt (retention time): 3.08 min; MS: (ES) m/z 477 (M+H+).

Workup

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

Sources & evidence

ORD record
ord-4c552b11ad6544d8b955b567e7c592ec
Source dataset
uspto-grants-2012_10
Patent number
US08293925B2

Reaction notes

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