Pyridine → 5-(1-Methanesulfonyl-piperidin-4-yloxy)-pyridine-2-sulfonic acid (4-fluoro-benzyl)-isobutyl-amide

HRID 1049043Notes

Reaction equation

HRID 1049043 reaction equation
[F:1][C:2]1[CH:13]=[CH:12][C:5]([CH2:6][NH:7][CH2:8][CH:9]([CH3:11])[CH3:10])=[CH:4][CH:3]=1.N1C=CC=CC=1.[CH3:20][S:21]([N:24]1[CH2:29][CH2:28][CH:27]([O:30][C:31]2[CH:32]=[CH:33][C:34]([S:37](Cl)(=[O:39])=[O:38])=[N:35][CH:36]=2)[CH2:26][CH2:25]1)(=[O:23])=[O:22]>C(Cl)Cl>[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][N:7]([CH2:8][CH:9]([CH3:11])[CH3:10])[S:37]([C:34]2[CH:33]=[CH:32][C:31]([O:30][CH:27]3[CH2:28][CH2:29][N:24]([S:21]([CH3:20])(=[O:22])=[O:23])[CH2:25][CH2:26]3)=[CH:36][N:35]=2)(=[O:38])=[O:39])=[CH:12][CH:13]=1

Participants

5

Reactant 3

HCID 1049PyridineHCID 966924(4-Fluorobenzyl)isobutylamineHCID 867218895-(1-Methanesulfonyl-piperidin-4-yloxy)-pyridine-2-sulfonyl chloride

Product 1

HCID 762844395-(1-Methanesulfonyl-piperidin-4-yloxy)-pyridine-2-sulfonic acid (4-fluoro-benzyl)-isobutyl-amideYield 37%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution of (4-fluorobenzyl)-isobutylamine (53 mg, 0.295 mmol) and pyridine (34 μL, 0.423 mmol) in DCM (3 mL) was treated with 5-(1-methanesulfonyl-piperidin-4-yloxy)-pyridine-2-sulfonyl chloride (75 mg, 0.211 mmol) and stirred at room temperature for 18 hours. The mixture was diluted with DCM, washed with 1 M aqueous citric acid, saturated aqueous NaHCO3, water and brine, dried over Na2SO4 and concentrated under vacuum. Purification by silica gel column chromatography (0-100% EtOAc in cyclohexane) and re-purification by silica gel column chromatography (0-10% EtOAc in DCM) to give the title compound (39 mg, 37%). 1H NMR (400 MHz, DMSO) δ 8.45 (d, J=2.8 Hz, 1H), 7.89 (d, J=8.7 Hz, 1H), 7.66 (dd, J=8.8, 2.9 Hz, 1H), 7.38-7.32 (m, 2H), 7.17-7.09 (m, 2H), 4.84-4.76 (m, 1H), 4.39 (s, 2H), 3.43-3.34 (m, 2H), 3.18-3.10 (m, 2H), 3.00 (d, J=7.5 Hz, 2H), 2.92 (s, 3H), 2.11-2.01 (m, 2H), 1.84-1.73 (m, 2H), 1.63-1.52 (m, 1H), 0.68 (d, J=6.6 Hz, 6H). LCMS (m/z, Method B) ES+ 499.9 [M+1]+.

Workup

  1. washwashed with 1 M aqueous citric acid, saturated aqueous NaHCO3, water and brine
  2. dry with materialdried over Na2SO4
  3. concentrationconcentrated under vacuum
  4. customPurification
  5. customby silica gel column chromatography (0-100% EtOAc in cyclohexane) and re-purification by silica gel column chromatography (0-10% EtOAc in DCM)

Sources & evidence

ORD record
ord-71ae0a00258f49a6afca6c3e787d6ce8
Source dataset
uspto-grants-2016_07
Patent number
US09382222B2

Reaction notes

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