Ethanol → 3-chloro-N-[4-(3'-cyano-biphenyl-4-yl)-1-cyclopropylmethyl-piperidin-4-ylmethyl]-4-fluoro-benzenesulfonamide

HRID 2180175Notes

Reaction equation

HRID 2180175 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([S:9]([NH:12][CH2:13][C:14]2([C:24]3[CH:29]=[CH:28][C:27](I)=[CH:26][CH:25]=3)[CH2:19][CH2:18][N:17]([CH2:20][CH:21]3[CH2:23][CH2:22]3)[CH2:16][CH2:15]2)(=[O:11])=[O:10])[CH:5]=[CH:6][C:7]=1[F:8].[C:31]([C:33]1[CH:34]=[C:35](B(O)O)[CH:36]=[CH:37][CH:38]=1)#[N:32].C([O-])([O-])=O.[Na+].[Na+].CCO>C1(C)C=CC=CC=1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O>[Cl:1][C:2]1[CH:3]=[C:4]([S:9]([NH:12][CH2:13][C:14]2([C:24]3[CH:29]=[CH:28][C:27]([C:37]4[CH:36]=[CH:35][CH:34]=[C:33]([C:31]#[N:32])[CH:38]=4)=[CH:26][CH:25]=3)[CH2:19][CH2:18][N:17]([CH2:20][CH:21]3[CH2:23][CH2:22]3)[CH2:16][CH2:15]2)(=[O:11])=[O:10])[CH:5]=[CH:6][C:7]=1[F:8]

Participants

8

Reactant 4

HCID 702EthanolHCID 10340Sodium CarbonateHCID 27343253-Cyanophenylboronic acidHCID 685368553-chloro-N-[1-cyclopropylmethyl-4-(4-iodo-phenyl)-piperidin-4-ylmethyl]-4-fluorobenzenesulfonamide

Product 1

HCID 207794453-chloro-N-[4-(3'-cyano-biphenyl-4-yl)-1-cyclopropylmethyl-piperidin-4-ylmethyl]-4-fluoro-benzenesulfonamideYield 450.7%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

To a flask containing 3-chloro-N-[1-cyclopropylmethyl-4-(4-iodo-phenyl)-piperidin-4-ylmethyl]-4-fluorobenzenesulfonamide (0.047 g, 0.04 mmol) was added Pd(PPh3)4 (0.005 g, 0.004 mmol, 10 mol %), 3-cyanophenylboronic acid (0.01 g, 0.06 mmol, 1.5 eq.) and Na2CO3 (0.106 g, 1 mmol). The mixture was suspended in toluene (1.5 mL), EtOH (0.75 mL) and H2O (0.5 mL) and heated to 80° C. for 18 h. The reaction mixture was cooled to room temperature and partitioned between ethyl acetate (5 mL) and saturated Na2CO3 (5 mL). The organic layer was washed with saturated Na2CO3 (3×5 mL), saturated brine (2×5 mL), dried over anhydrous sodium sulfate, filtered and concentrated to give a brown solid which was purified by HPLC to give 3-chloro-N-[4-(3′-cyano-biphenyl-4-yl)-1-cyclopropylmethyl-piperidin-4-ylmethyl]-4-fluoro-benzenesulfonamide (0.097 g, 45%). MS (ESI): 538.2/540.2.

Workup

  1. custompartitioned between ethyl acetate (5 mL) and saturated Na2CO3 (5 mL)
  2. washThe organic layer was washed with saturated Na2CO3 (3×5 mL), saturated brine (2×5 mL)
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto give a brown solid which
  7. customwas purified by HPLC

Sources & evidence

ORD record
ord-91067b2ceb104f6bafff75c6040098eb
Source dataset
uspto-grants-2005_05
Patent number
US06887889B2

Reaction notes

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