Sodium Carbonate → 5-[2-chloro-5-(4,4-dimethyl-3,4-dihydro-2H-quinoline-1-sulfonyl)-4-(4-hydroxy-butoxy)-phenyl]-2-trifluoromethyl-isonicotinonitrile

HRID 1891372Notes

Reaction equation

HRID 1891372 reaction equation
[Cl:1][C:2]1[C:3](B2OC(C)(C)C(C)(C)O2)=[CH:4][C:5]([S:14]([N:17]2[C:26]3[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=3)[C:20]([CH3:28])([CH3:27])[CH2:19][CH2:18]2)(=[O:16])=[O:15])=[C:6]([CH:13]=1)[O:7][CH2:8][CH2:9][CH2:10][CH2:11][OH:12].Br[C:39]1[C:44]([C:45]#[N:46])=[CH:43][C:42]([C:47]([F:50])([F:49])[F:48])=[N:41][CH:40]=1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.O.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>[Cl:1][C:2]1[CH:13]=[C:6]([O:7][CH2:8][CH2:9][CH2:10][CH2:11][OH:12])[C:5]([S:14]([N:17]2[C:26]3[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=3)[C:20]([CH3:27])([CH3:28])[CH2:19][CH2:18]2)(=[O:15])=[O:16])=[CH:4][C:3]=1[C:39]1[C:44]([C:45]#[N:46])=[CH:43][C:42]([C:47]([F:49])([F:50])[F:48])=[N:41][CH:40]=1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 569733155-Bromo-2-(trifluoromethyl)isonicotinonitrileHCID 684692424-[5-Chloro-2-(4,4-dimethyl-3,4-dihydro-2H-quinoline-1-sulfonyl)-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenoxy]-butan-1-ol

Product 1

HCID 251551005-[2-chloro-5-(4,4-dimethyl-3,4-dihydro-2H-quinoline-1-sulfonyl)-4-(4-hydroxy-butoxy)-phenyl]-2-trifluoromethyl-isonicotinonitrileYield 35.5%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 4-[5-Chloro-2-(4,4-dimethyl-3,4-dihydro-2H-quinoline-1-sulfonyl)-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenoxy]-butan-1-ol (270.0 mg, 0.49 mmol), 5-bromo-2-trifluoromethyl-isonicotinonitrile (112 mg, 0.45 mmol), Pd(Ph3P)4 (57 mg, 0.05 mmol) and Na2CO3 (286 mg, 2.7 mmol) in dioxane (4 mL) and water (0.4 mL) was degassed with N2 for 5 min. The reaction vessel was sealed and then heated at 100° C. for 16 hrs. The mixture was then partitioned between ethyl acetate (20 mL) and water (10 mL). The organic layer was washed with brine (2×10 mL), dried over MgSO4, filtered and concentrated to give a material which was purified by TLC plates eluting with 30% acetone in hexanes to give 5-[2-chloro-5-(4,4-dimethyl-3,4-dihydro-2H-quinoline-1-sulfonyl)-4-(4-hydroxy-butoxy)-phenyl]-2-trifluoromethyl-isonicotinonitrile 11-1 as a white solid (95 mg). MS: 594.2 (M+H)+; tR=2.94 min (method 1).

Workup

  1. customwas degassed with N2 for 5 min
  2. customThe reaction vessel was sealed
  3. customThe mixture was then partitioned between ethyl acetate (20 mL) and water (10 mL)
  4. washThe organic layer was washed with brine (2×10 mL)
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto give a material which
  9. customwas purified by TLC plates
  10. washeluting with 30% acetone in hexanes

Sources & evidence

ORD record
ord-69054c0ca2d745109acc18fc5f1266d5
Source dataset
uspto-grants-2013_08
Patent number
US08507536B2

Reaction notes

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