Piperidin-4-ol → 1-(4-(4-Bromophenylsulfonyl)phenyl)-3-(3-((4-hydroxypiperidin-1-yl)(imino)methyl)phenyl)urea

HRID 1797935Notes

Reaction equation

HRID 1797935 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([C:11]2[CH:16]=[CH:15][C:14]([NH:17][C:18]([NH:20][C:21]3[CH:26]=[CH:25][CH:24]=[C:23]([C:27]#[N:28])[CH:22]=3)=[O:19])=[CH:13][CH:12]=2)(=[O:10])=[O:9])=[CH:4][CH:3]=1.C(C1C=C(NC(=O)N)C=CC=1)#N.[NH:41]1[CH2:46][CH2:45][CH:44]([OH:47])[CH2:43][CH2:42]1>Cl.O1CCOCC1.CO>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([S:8]([C:11]2[CH:12]=[CH:13][C:14]([NH:17][C:18]([NH:20][C:21]3[CH:26]=[CH:25][CH:24]=[C:23]([C:27]([N:41]4[CH2:46][CH2:45][CH:44]([OH:47])[CH2:43][CH2:42]4)=[NH:28])[CH:22]=3)=[O:19])=[CH:15][CH:16]=2)(=[O:10])=[O:9])=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 79341Piperidin-4-olHCID 206364711-(3-Cyanophenyl)ureaHCID 57504036HCID 57504036, compound

Product 1

HCID 575040281-(4-(4-Bromophenylsulfonyl)phenyl)-3-(3-((4-hydroxypiperidin-1-yl)(imino)methyl)phenyl)urea

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 21966525Dioxane MethanolSolvent

Procedure

Under argon atmosphere, 1 equivalent of 1-(4-(4-bromophenylsulfonyl)phenyl)-3-(3-cyanophenyl)urea (VIII) [or a correspondent 14444-substituted-phenylsulfonyl)phenyl)-3-(3-cyanophenyl)urea] was dissolved in of 4 M HCl in dioxane/MeOH 5:1. The solution was stirred overnight at rt then the solvent was removed in vacuo. The residue was washed with diethylether, dried in vacuo, dissolved in dry MeOH (or DMF) and reacted with 1.1 to 2 equivalents of piperidin-4-ol (or 1.1 to 2 equivalents of the corresponding secondary amine) at temperature between 55 and 70° C. for a minimum of 4 h to a maximum of 22 h. The products were purified either by flash chromatography, using a silica gel column and an appropriate gradient of MeOH in DCM as eluent, or by preparative HPLC, using a reverse-phase column and a gradient of acetonitrile in 0.1% HCOOHaq.

Workup

  1. customthe solvent was removed in vacuo
  2. washThe residue was washed with diethylether
  3. customdried in vacuo
  4. dissolutiondissolved in dry MeOH (or DMF)
  5. customThe products were purified either by flash chromatography

Sources & evidence

ORD record
ord-26a1059800b6428da30c7c35f22aad99
Source dataset
uspto-grants-2013_01
Patent number
US08343963B2

Reaction notes

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