Methanesulfonyl chloride → 3-(1-Methylsulfonyl-trans-4-(2-pyridyl)-pyrrolidin-3-ylamino)-6-chloro-1-ethoxycarbonylmethylpyrazinone

HRID 398403Notes

Reaction equation

C(OC([N:8]1[CH2:12][C@@H:11]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][N:14]=2)[C@H:10]([NH:19][C:20]2[C:21](=[O:33])[N:22]([CH2:27][C:28]([O:30][CH2:31][CH3:32])=[O:29])[C:23]([Cl:26])=[CH:24][N:25]=2)[CH2:9]1)=O)(C)(C)C.CCN(C(C)C)C(C)C.[CH3:43][S:44](Cl)(=[O:46])=[O:45]>C(Cl)Cl.C([O-])(O)=O.[Na+]>[CH3:43][S:44]([N:8]1[CH2:12][C@@H:11]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][N:14]=2)[C@H:10]([NH:19][C:20]2[C:21](=[O:33])[N:22]([CH2:27][C:28]([O:30][CH2:31][CH3:32])=[O:29])[C:23]([Cl:26])=[CH:24][N:25]=2)[CH2:9]1)(=[O:46])=[O:45]

Participants

Conditions

Temperature: 0 °C

Procedure

To a stirred solution of the hydrochloride salt of 3-(trans-4-(2-pyridyl)-pyrrolidin-3-ylamino)-6-chloro-1-ethoxycarbonylmethylpyrazinone from step 9 above (0.2 g, 0.48 mmol) in CH2Cl2 (20 mL) at 0° C. was added DIEA (0.30 mL, 1.7 mmol) and methanesulfonyl chloride (63 mg, 0.55 mmol). The resulting solution was stirred at 0° C. for 6 h and then at ambient temperature for 12 h. The mixture was diluted with CH2Cl2 and aqueous NaHCO3. The organic phase was separated, dried over MgSO4, filtered, and concentrated in vacuo. The residue was purified by column chromatography using a gradient elution of 2-4% MeOH:CH2Cl2 (0.20 g, TLC Rf=0.5, 95:5 CH2Cl2:MeOH; HPLC RT=5.47 min, method A).

Workup

waitat ambient temperature for 12 h
customThe organic phase was separated
dry with materialdried over MgSO4
filtrationfiltered
concentrationconcentrated in vacuo
customThe residue was purified by column chromatography
washa gradient elution of 2-4% MeOH

Sources & evidence

ORD record: ord-156ef01714234d819d16f74ce98d78b7
Source dataset: uspto-grants-2003_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06610692B1

Reaction notes

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