Triethylamine → N-hydroxy-4-(4-(3-(3-(4-(trifluoromethoxy)phenyl)-1,2,4-oxadiazol-5-yl)propoxy)phenylsulfonyl)tetrahydro-2H-pyran-4-carboxamide

HRID 2181386Notes

Reaction equation

HRID 2181386 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.[F:48][C:49]([F:62])([F:61])[O:50][C:51]1[CH:60]=[CH:59][C:54]([C:55](=[N:57]O)[NH2:56])=[CH:53][CH:52]=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][N:57]=[C:55]([C:54]4[CH:59]=[CH:60][C:51]([O:50][C:49]([F:62])([F:61])[F:48])=[CH:52][CH:53]=4)[N:56]=3)=[CH:13][CH:12]=2)(=[O:15])=[O:16])[CH2:18][CH2:19][O:20][CH2:21][CH2:22]1)=[O:24]

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27333094-(Trifluoromethoxy)benzamidoximeHCID 27960291-Hydroxybenzotriazole hydrateHCID 865907724-[[4-(3-carboxypropoxy)phenyl]sulfonyl]tetrahydro-2H-pyran-4-carboxylic acid, 1,1-dimethylethyl ester

Product 1

HCID 22484431N-hydroxy-4-(4-(3-(3-(4-(trifluoromethoxy)phenyl)-1,2,4-oxadiazol-5-yl)propoxy)phenylsulfonyl)tetrahydro-2H-pyran-4-carboxamideYield 88.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Part A. In dry equipment under nitrogen, 4-[[4-(3carboxypropoxy)phenyl]sulfonyl]tetrahydro-2H-pyran-4-carboxylic acid, 1,1-dimethylethyl ester (2.57 g, 6.0 mmol, prepared as in Example 7) was dissolved in dry N,N-dimethylformamide (12 mL), and the remaining reagents were added to the solution in the following order: 1-hydroxybenzotriazole hydrate (1.13 g, 8.4 mmol), triethylamine (1.0 mL, 7.2 mmol), 4-(trifluoromethoxy)benzamidoxime (1.58 g, 7.2 mmol), and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (1.73 g, 9.0 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 afforded 3.05 g (81%) of the desired product as a clear glass. ESMS m/z=631 [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. concentrationconcentrated in vacuo
  7. customPurification by flash column chromatography

Sources & evidence

ORD record
ord-5a3a713f91d6438eb7176ed7ecdfd66e
Source dataset
uspto-grants-2005_05
Patent number
US06890928B2

Reaction notes

Loading…