N,N-dimethyl-p-phenylenediamine → HCID 131724876, compound

HRID 2181384Notes

Reaction equation

HRID 2181384 reaction equation
[C:1]([CH2:4][CH2:5][CH2:6][CH2:7][O:8][C:9]1[CH:14]=[CH:13][C:12]([S:15]([C:18]2([C:24]([O:26]C(C)(C)C)=O)[CH2:23][CH2:22][O:21][CH2:20][CH2:19]2)(=[O:17])=[O:16])=[CH:11][CH:10]=1)([OH:3])=O.[OH:31][N:32]1C2C=CC=CC=2N=N1.C(N(CC)CC)C.[CH3:48][N:49]([CH3:57])[C:50]1[CH:55]=[CH:54][C:53]([NH2:56])=[CH:52][CH:51]=1.[ClH:58].CN(C)CCCN=C=NCC>CN(C)C=O>[ClH:58].[CH3:48][N:49]([CH3:57])[C:50]1[CH:55]=[CH:54][C:53]([NH:56][C:1](=[O:3])[CH2:4][CH2:5][CH2:6][CH2:7][O:8][C:9]2[CH:10]=[CH:11][C:12]([S:15]([C:18]3([C:24]([NH:32][OH:31])=[O:26])[CH2:23][CH2:22][O:21][CH2:20][CH2:19]3)(=[O:17])=[O:16])=[CH:13][CH:14]=2)=[CH:52][CH:51]=1

Participants

7

Reactant 5

HCID 7472N,N-dimethyl-p-phenylenediamineHCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 91208993HCID 91208993, compound

Product 1

HCID 131724876HCID 131724876, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Part A. To a solution of 4-[[4-(4-carboxybutoxy)phenyl]sulfonyl]tetrahydro-2H-pyran-4-carboxylic acid, 1,1-dimethylethyl ester (446 mg, 0.91 mmol, prepared as in Example 7) in anhydrous N,N-dimethylformamide (6 mL) was added 1-hydroxybenzotriazole (150 mg, 1.11 mmol), triethylamine (400 uL, 2.87 mmol), N,N-dimethyl-1,4-phenylenediamine (188 mg, 1.38 mmol), and finally 1-(3-dimethyaminopropyl)-3-ethylcarbodiimide hydrochloride (300 mg, 1.56 mmol). The reaction mixture was stirred at ambient temperature for 18 hr, and then concentrated in vacuo at 60° C. The residue was partitioned between ethyl acetate and saturated sodium bicarbonate solution. The organic layer was washed with brine (2×), dried over sodium sulfate, filtered, and concentrated in vacuo to give the desired amide. ESMS m/z=561 [M+H]+. This material was taken up in neat trifluoroacetic acid (5 mL). After 3 hr the trifluoroacetic acid was removed in vacuo at 60° C. to give the free acid. ESMS m/z=505 [M+H]+. To a solution of this material in anhydrous N,N-dimethylformamide (5 mL) was added 1-hydroxybenzotriazole (148 mg, 1.10 mmol), triethylamine (400 uL, 2.87 mmol), and tetrahydropyranhydroxylamine (320 mg, 2.73 mmol), followed by 1-(3-dimethyaminopropyl)-3-ethylcarbodiimide hydrochloride (262 mg, 1.37 mmol). The reaction mixture was stirred at ambient temperature overnight, and then partitioned between ethyl acetate and saturated sodium bicarbonate solution. The organic layer was washed with brine (3×), dried over sodium sulfate, filtered, and concentrated in vacuo. The crude material was purified by flash chromatography using 80% ethyl acetate/hexanes as eluant to afford the desired THP hydroxamate. ESMS m/z=604 [M+H]+. HRMS calculated for C30H41N3O8S: 604.2693 [M+H]+. found: 604.2709.

Workup

  1. concentrationconcentrated in vacuo at 60° C
  2. customThe residue was partitioned between ethyl acetate and saturated sodium bicarbonate solution
  3. washThe organic layer was washed with brine (2×)
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-889674bc4662469ab70124c1d4d6a226
Source dataset
uspto-grants-2005_05
Patent number
US06890928B2

Reaction notes

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