Triethylamine → tetrahydro-N-hydroxy-4-[[4-[3-[5-(2-methylphenyl)-1,3,4-oxadiazol-2-yl]propoxy]phenyl]sulfonyl]-2H-pyran-4-carboxamide

HRID 2181387Notes

Reaction equation

HRID 2181387 reaction equation
[C:1]([CH2:4][CH2:5][CH2:6][O:7][C:8]1[CH:13]=[CH:12][C:11]([S:14]([C:17]2([C:23](OC(C)(C)C)=[O:24])[CH2:22][CH2:21][O:20][CH2:19][CH2:18]2)(=[O:16])=[O:15])=[CH:10][CH:9]=1)(O)=[O:2].O.[OH:31][N:32]1C2C=CC=CC=2N=N1.C(N(CC)CC)C.[C:48]1([CH3:58])[C:49]([C:54]([NH:56][NH2:57])=O)=[CH:50][CH:51]=[CH:52][CH:53]=1.Cl.CN(C)CCCN=C=NCC>CN(C)C=O>[OH:31][NH:32][C:23]([C:17]1([S:14]([C:11]2[CH:10]=[CH:9][C:8]([O:7][CH2:6][CH2:5][CH2:4][C:1]3[O:2][C:54]([C:49]4[CH:50]=[CH:51][CH:52]=[CH:53][C:48]=4[CH3:58])=[N:56][N:57]=3)=[CH:13][CH:12]=2)(=[O:16])=[O:15])[CH2:22][CH2:21][O:20][CH2:19][CH2:18]1)=[O:24]

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 82110o-ToluohydrazideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 865907724-[[4-(3-carboxypropoxy)phenyl]sulfonyl]tetrahydro-2H-pyran-4-carboxylic acid, 1,1-dimethylethyl ester

Product 1

HCID 22484429tetrahydro-N-hydroxy-4-[[4-[3-[5-(2-methylphenyl)-1,3,4-oxadiazol-2-yl]propoxy]phenyl]sulfonyl]-2H-pyran-4-carboxamideYield 92.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Part A. In dry equipment under nitrogen, 4-[[4-(3-carboxypropoxy)phenyl]sulfonyl]tetrahydro-2H-pyran-4-carboxylic acid, 1,1-dimethylethyl ester (2.14 g, 5.0 mmol, prepared as in Example 7) was dissolved in dry N,N-dimethylformamide (10 mL), and the remaining reagents were added to the solution in the following order: 1-hydroxybenzotriazole hydrate (945 mg, 7.0 mmol), triethylamine (0.84 mL, 6.0 mmol), o-toluic hydrazide (901 mg, 6.0 mmol), and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (1.44 g, 7.5 mmol). After 2 hr at 35° C., the reaction was concentrated in vacuo. The residue was taken up in ethyl acetate; washed with water, saturated sodium bicarbonate solution, and brine; dried over sodium sulfate; filtered; and concentrated in vacuo. Purification by flash column chromatography using ethyl acetate/hexanes provided 2.32 g (83%) of the desired product as a white foam. ESMS m/z=583 [M+Na]+.

Workup

  1. additionthe remaining reagents were added to the solution in the following order
  2. concentrationthe reaction was concentrated in vacuo
  3. washwashed with water, saturated sodium bicarbonate solution, and brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationand concentrated in vacuo
  7. customPurification by flash column chromatography

Sources & evidence

ORD record
ord-611dcda2a2df4e19a6c6f906948f04b3
Source dataset
uspto-grants-2005_05
Patent number
US06890928B2

Reaction notes

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