1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → (2R)-2-methyl-4-(3-methyl-4-phenyl-1H-pyrazol-1-yl)-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide

HRID 2405921Notes

Reaction equation

HRID 2405921 reaction equation
[CH3:1][C@@:2]([S:20]([CH3:23])(=[O:22])=[O:21])([CH2:6][CH2:7][N:8]1[CH:12]=[C:11]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[C:10]([CH3:19])=[N:9]1)[C:3]([OH:5])=O.CCN(C(C)C)C(C)C.C1C=CC2N(O)N=NC=2C=1.[O:43]1[CH2:48][CH2:47][CH2:46][CH2:45][CH:44]1[O:49][NH2:50].CCN=C=NCCCN(C)C>C(Cl)Cl>[CH3:1][C@@:2]([S:20]([CH3:23])(=[O:22])=[O:21])([CH2:6][CH2:7][N:8]1[CH:12]=[C:11]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[C:10]([CH3:19])=[N:9]1)[C:3]([NH:50][O:49][CH:44]1[CH2:45][CH2:46][CH2:47][CH2:48][O:43]1)=[O:5]

Participants

7

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 5142091O-(Tetrahydropyran-2-yl)hydroxylamineHCID 70817777(2R)-2-methyl-4-(3-methyl-4-phenyl-1H-pyrazol-1-yl)-2-(methylsulfonyl)butanoic acid

Product 1

HCID 86710235(2R)-2-methyl-4-(3-methyl-4-phenyl-1H-pyrazol-1-yl)-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamideYield 66.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (2R)-2-methyl-4-(3-methyl-4-phenyl-1H-pyrazol-1-yl)-2-(methylsulfonyl)butanoic acid (129 mg, 0.38 mmol, 1 eq) in anhydrous DCM (7 mL) was added DIPEA (140 uL, 0.804 mmol, 2.1 eq), followed by HOBt (120 mg, 0.784 mmol, 2.05 eq) and the solution was stirred at RT for 30 minutes. The mixture was then treated with O-tetrahydro-2H-pyran-2-yl-hydroxylamine (70 mg, 0.60 mmol, 1.6 eq) followed by EDCI (110 mg, 0.574 mmol, 1.5 eq) and the reaction was allowed to stir at RT. The reaction mixture was concentrated in vacuo to give a crude white solid. The crude mixture was purified via flash chromatography using an Analogix SF15-12 g silica column eluting with ethyl acetate in heptane (0-80%) to give (2R)-2-methyl-4-(3-methyl-4-phenyl-1H-pyrazol-1-yl)-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide (110 mg, 66% yield). LC-MS M+H+436.1.

Workup

  1. stirringto stir at RT
  2. concentrationThe reaction mixture was concentrated in vacuo
  3. customto give a crude white solid
  4. customThe crude mixture was purified via flash chromatography
  5. washeluting with ethyl acetate in heptane (0-80%)

Sources & evidence

ORD record
ord-fa93809220df4d2baddf9606b7f8f661
Source dataset
uspto-grants-2014_08
Patent number
US08809333B2

Reaction notes

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