Diisopropylethylamine → 2-Ethyl-2-(methylsulfonyl)-4-(2-oxo-4-phenylpyridin-1(2H)-yl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide

HRID 1183992Notes

Reaction equation

HRID 1183992 reaction equation
C(N(C(C)C)CC)(C)C.O.ON1C2C=CC=CC=2N=N1.[CH2:21]([C:23]([S:42]([CH3:45])(=[O:44])=[O:43])([CH2:27][CH2:28][N:29]1[CH:34]=[CH:33][C:32]([C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)=[CH:31][C:30]1=[O:41])[C:24]([OH:26])=O)[CH3:22].[O:46]1[CH2:51][CH2:50][CH2:49][CH2:48][CH:47]1[O:52][NH2:53].Cl.CN(C)CCCN=C=NCC>ClCCl.O>[CH2:21]([C:23]([S:42]([CH3:45])(=[O:43])=[O:44])([CH2:27][CH2:28][N:29]1[CH:34]=[CH:33][C:32]([C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)=[CH:31][C:30]1=[O:41])[C:24]([NH:53][O:52][CH:47]1[CH2:48][CH2:49][CH2:50][CH2:51][O:46]1)=[O:26])[CH3:22]

Participants

8

Reactant 5

HCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 5142091O-(Tetrahydropyran-2-yl)hydroxylamineHCID 672483492-Ethyl-2-(methylsulfonyl)-4-(2-oxo-4-phenylpyridin-1(2H)-yl)butanoic acid

Product 1

HCID 866719552-Ethyl-2-(methylsulfonyl)-4-(2-oxo-4-phenylpyridin-1(2H)-yl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamideYield 108.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

Diisopropylethylamine (35 uL, 0.2 mmol, 2.1 equiv) and 1-hydroxyl benzotriazole monohydrate (27 mg, 0.18 mmol, 1.9 equiv) were added sequentially to a solution of 2-ethyl-2-(methylsulfonyl)-4-(2-oxo-4-phenylpyridin-1(2H)-yl)butanoic acid (34 mg, 0.09 mmol, 1.0 equiv) in dichloromethane (2 mL) at room temperature. After 30 min, O-(tetrahydro-2H-pyran-2-yl)hydroxylamine (15 mg, 0.12 mmol, 1.3 equiv) and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (26 mg, 0.13 mmol, 1.4 equiv) were added, and the reaction was allowed to stir overnight. Water (2 mL) was added, the organic phase was separated, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The crude material was purified by flash chromatography (1:1-0:1 heptane/ethyl acetate) to provide a colorless oil (45 mg, 100%). MS (LCMS) m/z 461.8 (M−1).

Workup

  1. customthe organic phase was separated
  2. dry with materialdried over anhydrous magnesium sulfate
  3. concentrationconcentrated under reduced pressure
  4. customThe crude material was purified by flash chromatography (1:1-0:1 heptane/ethyl acetate)

Sources & evidence

ORD record
ord-52163ca02cf743c9918b9df6502de165
Source dataset
uspto-grants-2014_03
Patent number
US08664401B2

Reaction notes

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