Triethylamine → HCID 25241875, compound

HRID 2197583Notes

Reaction equation

HRID 2197583 reaction equation
FC(F)(F)S(O[C:7]1[CH2:12][CH2:11][C:10]([C:14]2[C:19]([Cl:20])=[CH:18][CH:17]=[CH:16][N:15]=2)([F:13])[CH2:9][CH:8]=1)(=O)=O.[F:23][C:24]([F:33])([F:32])[C:25]1[CH:31]=CC(N)=[CH:27][CH:26]=1.C([N:36]([CH2:39]C)[CH2:37][CH3:38])C.C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2N(C)C)CCCCC1.[C]=[O:70]>CN(C)C=O.ClCCl.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(OCC)(=O)C>[Cl:20][C:19]1[C:14]([C:10]2([F:13])[CH2:11][CH2:12][C:7]([C:39]([NH:36][C:37]3[CH:38]=[CH:31][C:25]([C:24]([F:33])([F:32])[F:23])=[CH:26][CH:27]=3)=[O:70])=[CH:8][CH2:9]2)=[N:15][CH:16]=[CH:17][CH:18]=1

Participants

10

Reactant 5

HCID 8471TriethylamineHCID 99644-(Trifluoromethyl)anilineHCID 27342172-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenylHCID 86630279HCID 86630279, compoundHCID 178418416HCID 178418416, compound

Product 1

HCID 25241875HCID 25241875, compoundYield 81%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

A mixture of the product of Example 1D (1.590 g, 4.42 mmol), 4-(trifluoromethyl)aniline (1.424 g, 8.84 mmol), and triethylamine (1.24 mL, 8.90 mmol) in dimethylformamide (30 mL) was added to palladium(II) acetate (49.3 mg, 0.220 mmol) and 2-dicyclohexylphosphino-2′-(dimethylamino)biphenyl (174.7 mg, 0.444 mmol) in a 250 mL pressure bottle under argon. The mixture was pressurized with carbon monoxide (60 psi), stirred 14 hours at ambient temperature, treated with ethyl acetate (200 mL), washed with saturated sodium bicarbonate (200 mL), brine, dried with anhydrous sodium sulfate, filtered, and concentrated. The residue was chromatographed on silica gel, eluting with 0-to-40% ethyl acetate in hexanes, and concentrated to a yellow oil. Repeated chromatography on silica gel, eluting with dichloromethane, then 30% ethyl acetate in dichloromethane afforded 1.424 g (81% yield) of the title compound as a light yellow solid. 1H NMR (300 MHz, DMSO-d6) δ ppm 2.15-2.36 (m, 1H), 2.89-3.01 (m, 1H), 3.08-3.21 (m, 1H), 6.75 (s, 1H), 7.49 (ddd, J=8.13, 4.56, 0.79 Hz, 1H), 7.68 (d, J=8.33 Hz, 2H), 7.93 (d, J=8.33 Hz, 2H), 8.03 (dd, J=8.13, 1.39 Hz, 1H), 8.56 (d, J=4.76 Hz, 1H), 10.10 (s, 1H). 1H NMR (300 MHz, CDCl3) δ ppm 2.26-2.47 (m, 1H), 2.55-2.72 (m, 3H), 2.93-3.05 (m, 1H), 3.15-3.33 (m, 1H), 6.74 (s, 1H), 7.22-7.27 (m, 1H), 7.58-7.61 (m, 3H), 7.71 (d, J=8.47 Hz, 2H), 7.77 (dd, J=8.13, 1.35 Hz, 1H), 8.46 (ddd, J=4.58, 1.52, 0.85 Hz, 1H). MS (ESI) m/z 398.95 (M+H)+. Calcd for C19H15ClF4N2O: C, 57.23, H, 3.79, N, 7.02. Found: C, 57.11; H, 3.49; N, 6.92.

Workup

  1. washwashed with saturated sodium bicarbonate (200 mL), brine
  2. dry with materialdried with anhydrous sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue was chromatographed on silica gel
  6. washeluting with 0-to-40% ethyl acetate in hexanes
  7. concentrationconcentrated to a yellow oil
  8. washeluting with dichloromethane

Sources & evidence

ORD record
ord-c7845ccf006f41118e82a398835eac55
Source dataset
uspto-grants-2012_12
Patent number
US08338603B2

Reaction notes

Loading…