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

HRID 2405953Notes

Reaction equation

HRID 2405953 reaction equation
[CH3:1][C:2]([S:19]([CH3:22])(=[O:21])=[O:20])([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)[N:10]=[CH:9]1)[C:3]([OH:5])=O.CCN=C=NCCCN(C)C.C1C=CC2[N:42]([OH:43])N=NC=2C=1.[O:44]1[CH2:49][CH2:48][CH2:47][CH2:46][CH:45]1NO>C(Cl)Cl.O>[CH3:1][C:2]([S:19]([CH3:22])(=[O:21])=[O:20])([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)[N:10]=[CH:9]1)[C:3]([NH:42][O:43][CH:45]1[CH2:46][CH2:47][CH2:48][CH2:49][O:44]1)=[O:5]

Participants

7

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 13168123Tetrahydropyranyl hydroxylamineHCID 708175182-methyl-2-(methylsulfonyl)-4-(4-phenyl-1H-imidazol-1-yl)butanoic acid

Product 1

HCID 867102522-methyl-2-(methylsulfonyl)-4-(4-phenyl-1H-imidazol-1-yl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamideYield 6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 2-methyl-2-(methylsulfonyl)-4-(4-phenyl-1H-imidazol-1-yl)butanoic acid (304.6 mg, 0.945 mmol, 1 eq) in DCM (10 mL) was added TEA (172 mg, 1.70 mmol, 0.237 mL, 1.80 eq), EDCI (254 mg, 1.32 mmol, 1.4 eq), HOBT (260 mg 1.70 mmol, 1.80 eq) and O— tetrahydro-2-H-pyran-2-ylhydroxylamine (166 mg, 1.42 mmol, 1.5 eq). The reaction was allowed stir at RT overnight. The reaction mixture was diluted with DCM and water. The aqueous layer was extracted several times with DCM and the combined organic layers were dried (MgSO4), filtered and concentrated. The crude product mixture was absorbed onto silica gel and purified by flash chromatrography on silica gel eluting with an EtOAc-heptane gradient to give 2-methyl-2-(methylsulfonyl)-4-(4-phenyl-1H-imidazol-1-yl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide (24 mg, 6% yield). LC-MS M+H+422.6.

Workup

  1. extractionThe aqueous layer was extracted several times with DCM
  2. dry with materialthe combined organic layers were dried (MgSO4)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe crude product mixture was absorbed onto silica gel
  6. custompurified by flash chromatrography on silica gel eluting with an EtOAc-heptane gradient

Sources & evidence

ORD record
ord-2235fbe2387e4b26a8fd0a1bbea7beec
Source dataset
uspto-grants-2014_08
Patent number
US08809333B2

Reaction notes

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