N-methyl-2-pyrrolidone → HCID 117629594, compound

HRID 920271Notes

Reaction equation

HRID 920271 reaction equation
Cl.[Cl:2][C:3]1[C:4]([S:27]([NH:30][C:31]2[S:35][N:34]=[CH:33][N:32]=2)(=[O:29])=[O:28])=[CH:5][C:6]2[O:10][C:9](=[O:11])[N:8]([C@@H:12]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=3[C:20]3[CH2:21][CH2:22][NH:23][CH2:24][CH:25]=3)[CH3:13])[C:7]=2[CH:26]=1.CN1C(=O)CCC1.CCN(C(C)C)C(C)C.[CH3:52][S:53](Cl)(=[O:55])=[O:54]>O>[Cl:2][C:3]1[C:4]([S:27]([NH:30][C:31]2[S:35][N:34]=[CH:33][N:32]=2)(=[O:29])=[O:28])=[CH:5][C:6]2[O:10][C:9](=[O:11])[N:8]([C@@H:12]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=3[C:20]3[CH2:21][CH2:22][N:23]([S:53]([CH3:52])(=[O:55])=[O:54])[CH2:24][CH:25]=3)[CH3:13])[C:7]=2[CH:26]=1

Participants

6

Reactant 4

HCID 13387N-methyl-2-pyrrolidoneHCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 89525975HCID 89525975, compound

Product 1

HCID 117629594HCID 117629594, compound

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To round bottom flask was added (R)-5-chloro-2-oxo-3-(1-(2-(1,2,3,6-tetrahydropyridin-4-yl)phenyl)ethyl)-N-(1,2,4-thiadiazol-5-yl)-2,3-dihydrobenzo[d]oxazole-6-sulfonamide hydrochloride (34-6) (10 mg, 0.018 mmol), followed by NMP (1 ml), then DIPEA (50 μl, 0.286 mmol), followed by METHANESULFONYL CHLORIDE (6.80 μl, 0.087 mmol). The reaction mixture was then capped (not under N2) & stirred at room temperature. Followed by LC/MS. After 2 minutes; the reaction mixture was diluted with H2O, then MeOH, & purified (without workup) by reverse phase chromatography (5-75% MeCN/H2O; 0.1% TFA in AQ; 20 min gradient; Waters 30×150 mm Sunfire 5 micron C18 column); desired fractions concentrated (GENEVAC), then dissolved in MeOH/DCM & concentrated to yield (R)-5-chloro-2-oxo-3-(1-(2-(1,2,3,6-tetrahydropyridin-4-yl)phenyl)ethyl)-N-(1,2,4-thiadiazol-5-yl)-2,3-dihydrobenzo-[d]oxazole-6-sulfonamide hydrochloride (36-1). MS [M+H] calculated; 596.1 observed; 596.0. 1H NMR (499 MHz, DMSO): δ 8.47 (s, 1H); 7.94 (s, 1H); 7.73 (d, J=7.8 Hz, 1H); 7.37 (d, J=7.6 Hz, 2H); 7.13 (d, J=9.8 Hz, 2H); 5.77-5.73 (m, 2H); 5.46 (s, 1H); 3.75-3.51 (m, 3H); 3.04-2.95 (m, 1H); 2.89 (s, 3H); 1.89-1.74 (m, 4H). Note: Peaks overlapping with water or solvent can not be accurately accounted for.

Workup

  1. customThe reaction mixture was then capped (not under N2) &
  2. customMeOH, & purified (without workup) by reverse phase chromatography (5-75% MeCN/H2O; 0.1% TFA in AQ; 20 min gradient; Waters 30×150 mm Sunfire 5 micron C18 column)
  3. concentrationdesired fractions concentrated (GENEVAC)
  4. dissolutiondissolved in MeOH/DCM
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-a2ab4b4d0db945a8b0df85b3bcb1941d
Source dataset
uspto-grants-2016_03
Patent number
US09273040B2

Reaction notes

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