Ethanesulfonyl chloride → 5'-chloro-N2'-(1-(ethylsulfonyl)piperidin-4-yl)-N6-(3-fluoro benzyl)-2,4'-bipyridine-2',6-diamine

HRID 1963863Notes

Reaction equation

HRID 1963863 reaction equation
[Cl:1][C:2]1[C:3]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([NH:21][CH2:22][C:23]3[CH:28]=[CH:27][CH:26]=[C:25]([F:29])[CH:24]=3)[N:16]=2)=[CH:4][C:5]([NH:8][CH:9]2[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]2)=[N:6][CH:7]=1.[CH2:30]([S:32](Cl)(=[O:34])=[O:33])[CH3:31]>ClCCl.CS(C)=O>[Cl:1][C:2]1[C:3]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([NH:21][CH2:22][C:23]3[CH:28]=[CH:27][CH:26]=[C:25]([F:29])[CH:24]=3)[N:16]=2)=[CH:4][C:5]([NH:8][CH:9]2[CH2:10][CH2:11][N:12]([S:32]([CH2:30][CH3:31])(=[O:34])=[O:33])[CH2:13][CH2:14]2)=[N:6][CH:7]=1

Participants

5

Reactant 2

HCID 11667Ethanesulfonyl chlorideHCID 601421355'-chloro-N6-(3-fluorobenzyl)-N2'-(piperidin-4-yl)-2,4'-bipyridine-2',6-diamine

Product 1

HCID 669368475'-chloro-N2'-(1-(ethylsulfonyl)piperidin-4-yl)-N6-(3-fluoro benzyl)-2,4'-bipyridine-2',6-diamineYield 50.4%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

A mixture of 5′-chloro-N6-(3-fluorobenzyl)-N2′-(piperidin-4-yl)-2,4′-bipyridine-2′,6-diamine (Example 6, 16 mg, 0.039 mmol), dichloromethane (0.5 ml), and TEA (0.022 ml, 0.155 mmol) was cooled to 0° C. This cooled mixture was then diluted with a solution of 0.03 ml of dichlormethane with ethanesulfonyl chloride (6.99 mg, 0.054 mmol). The reaction mixture then was warmed to ambient temperature and stirred for 1 hour, followed by LCMS. The reaction mixture solvent was removed under reduced pressure, to yield a residue which was dissolved in 0.75 ml DMSO, filtered, purified by prep LC and then lyophilized to yield 9.9 mg of the title compound, as a TFA salt. LCMS (m/z): 504.2 (MH+), retention time=0.77 min.; 1H NMR (300 MHz, METHANOL-d4, 25° C.) δ ppm 1.32 (t, J=7.33 Hz, 3 H) 1.47-1.67 (m, 2 H) 2.08 (d, J=10.84 Hz, 2 H) 2.96-3.12 (m, 4 H) 3.75 (d, J=12.89 Hz, 2 H) 3.80-3.92 (m, 1 H) 4.65 (s, 2 H) 6.83 (s, 1 H) 6.92 (d, J=9.08 Hz, 1 H) 6.95 (d, J=7.62 Hz, 1 H) 7.01 (t, J=8.64 Hz, 1 H) 7.11 (d, J=9.96 Hz, 1 H) 7.19 (d, J=7.62 Hz, 1 H) 7.30-7.41 (m, 1 H) 7.75-7.85 (m, 1 H) 8.06 (s, 1 H)

Workup

  1. temperatureThe reaction mixture then was warmed to ambient temperature
  2. customThe reaction mixture solvent was removed under reduced pressure
  3. customto yield a residue which
  4. filtrationfiltered
  5. custompurified by prep LC

Sources & evidence

ORD record
ord-04152d8301964eb98ac1fbf9d8609639
Source dataset
uspto-grants-2013_04
Patent number
US08415381B2

Reaction notes

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