Dimethylamine → (S)-5-chloro-6-(4-(3-(2-fluoro-4-(methylsulfonyl)phenylamino)-2-oxopyrrolidin-1-yl)piperidin-1-yl)-N,N-dimethylnicotinamide

HRID 408014Notes

Reaction equation

HRID 408014 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](Cl)=[O:8].[CH3:35][NH:36][CH3:37]>CN(C=O)C.C(#N)C.C1COCC1.CCOC(C)=O>[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]([N:36]([CH3:37])[CH3:35])=[O:8]

Participants

5

Reactant 2

HCID 674DimethylamineHCID 86688120(S)-5-chloro-6-(4-(3-(2-fluoro-4-(methylsulfonyl)phenylamino)-2-oxopyrrolidin-1-yl)piperidin-1-yl)nicotinoyl chloride

Product 1

HCID 54670712(S)-5-chloro-6-(4-(3-(2-fluoro-4-(methylsulfonyl)phenylamino)-2-oxopyrrolidin-1-yl)piperidin-1-yl)-N,N-dimethylnicotinamideYield 39.3%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 86691292Dmf acn thfSolvent

Procedure

To a solution of (S)-5-chloro-6-(4-(3-(2-fluoro-4-(methylsulfonyl)phenylamino)-2-oxopyrrolidin-1-yl)piperidin-1-yl)nicotinoyl chloride (0.15 g, 0.28 mmol) in 5 mL of DMF/ACN/THF (1:1:1) was added dimethylamine (2 M solution in THF, 1.4 mL, 2.8 mmol) and the reaction was stirred at ambient temperature for 4 hours. The reaction was diluted with EtOAc (100 mL) and the organic layer was washed with water (20 mL) and brine (20 mL), and the organic layer was dried over MgSO4, and concentrated under vacuum. The material was triturated with isopropanol (about 6 mL) to give (S)-5-chloro-6-(4-(3-(2-fluoro-4-(methylsulfonyl)phenylamino)-2-oxopyrrolidin-1-yl)piperidin-1-yl)-N,N-dimethylnicotinamide (0.059 g, 0.11 mmol, 38% yield). Mass spectrum (apci) m/z=538.0 (M+H).

Workup

  1. washthe organic layer was washed with water (20 mL) and brine (20 mL)
  2. dry with materialthe organic layer was dried over MgSO4
  3. concentrationconcentrated under vacuum
  4. customThe material was triturated with isopropanol (about 6 mL)

Sources & evidence

ORD record
ord-4f4b49fd18794cc582b2f033d713457f
Source dataset
uspto-grants-2014_06
Patent number
US08754226B2

Reaction notes

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