Thionyl Chloride → (S)-5-chloro-6-(4-(3-(2-fluoro-4-(methylsulfonyl)phenylamino)-2-oxopyrrolidin-1-yl)piperidin-1-yl)nicotinoyl chloride

HRID 408013Notes

Reaction equation

HRID 408013 reaction equation
[Cl:1][C:2]1[C:3]([N:11]2[CH2:16][CH2:15][CH:14]([N:17]3[CH2:21][CH2:20][C@H:19]([NH:22][C:23]4[CH:28]=[CH:27][C:26]([S:29]([CH3:32])(=[O:31])=[O:30])=[CH:25][C:24]=4[F:33])[C:18]3=[O:34])[CH2:13][CH2:12]2)=[N:4][CH:5]=[C:6]([CH:10]=1)[C:7](O)=[O:8].S(Cl)([Cl:37])=O>C(Cl)Cl.CN(C=O)C>[Cl:1][C:2]1[C:3]([N:11]2[CH2:16][CH2:15][CH:14]([N:17]3[CH2:21][CH2:20][C@H:19]([NH:22][C:23]4[CH:28]=[CH:27][C:26]([S:29]([CH3:32])(=[O:31])=[O:30])=[CH:25][C:24]=4[F:33])[C:18]3=[O:34])[CH2:13][CH2:12]2)=[N:4][CH:5]=[C:6]([CH:10]=1)[C:7]([Cl:37])=[O:8]

Participants

5

Reactant 2

HCID 24386Thionyl ChlorideHCID 86688119(S)-5-chloro-6-(4-(3-(2-fluoro-4-(methylsulfonyl)phenylamino)-2-oxopyrrolidin-1-yl)piperidin-1-yl)nicotinic acid

Product 1

HCID 86688120(S)-5-chloro-6-(4-(3-(2-fluoro-4-(methylsulfonyl)phenylamino)-2-oxopyrrolidin-1-yl)piperidin-1-yl)nicotinoyl chlorideYield 203.8%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution of (S)-5-chloro-6-(4-(3-(2-fluoro-4-(methylsulfonyl)phenylamino)-2-oxopyrrolidin-1-yl)piperidin-1-yl)nicotinic acid (0.40 g, 0.38 mmol) in DCM (20 mL) was added sulfurous dichloride (0.28 g, 2.3 mmol) and DMF (1 drop) and the reaction was stirred at ambient temperature for 3 hours. The reaction was concentrated under vacuum to give (S)-5-chloro-6-(4-(3-(2-fluoro-4-(methylsulfonyl)phenylamino)-2-oxopyrrolidin-1-yl)piperidin-1-yl)nicotinoyl chloride (0.41 g, 100%). The material was used directly in the next step without purification.

Workup

  1. concentrationThe reaction was concentrated under vacuum

Sources & evidence

ORD record
ord-01c3d18591d0460b902c8e00725a9fcc
Source dataset
uspto-grants-2014_06
Patent number
US08754226B2

Reaction notes

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