2-(Dicyclohexylphosphino)biphenyl → HCID 57829762, compound

HRID 1855419Notes

Reaction equation

HRID 1855419 reaction equation
C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2)CCCCC1.[CH3:26][O:27][C:28]1[CH:29]=[C:30]([NH2:40])[CH:31]=[CH:32][C:33]=1[N:34]1[CH:38]=[C:37]([CH3:39])[N:36]=[CH:35]1.Cl[C:42]1[N:47]=[C:46]([O:48][CH:49]2[CH2:53][CH2:52][CH2:51][CH2:50]2)[CH:45]=[C:44]([CH3:54])[N:43]=1.ClC1C=C(C)N=C(OC2CCCC2)N=1>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH:49]1([O:48][C:46]2[CH:45]=[C:44]([CH3:54])[N:43]=[C:42]([NH:40][C:30]3[CH:31]=[CH:32][C:33]([N:34]4[CH:38]=[C:37]([CH3:39])[N:36]=[CH:35]4)=[C:28]([O:27][CH3:26])[CH:29]=3)[N:47]=2)[CH2:50][CH2:51][CH2:52][CH2:53]1

Participants

7

Reactant 4

HCID 27342162-(Dicyclohexylphosphino)biphenylHCID 454801813-methoxy-4-(4-methyl-1H-imidazol-1-yl)anilineHCID 62476925HCID 62476925, compoundHCID 86633621HCID 86633621, compound

Product 1

HCID 57829762HCID 57829762, compoundYield 37%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
200 °C

Procedure

Palladium acetate (7.1 mg, 0.03 mmol) and 2-(dicyclohexylphosphino)biphenyl (23.1 mg, 0.64 mmol) were dissolved in dioxane (3.6 mL) and stirred for 10 minutes at. Sodium tert.-butylate (59 mg, 0.6 mmol), 3-methoxy-4-(4-methyl-imidazol-1-yl)-phenylamine (81 mg, 0.4 mmol) and 1:1 mixture of 2-chloro-4-cyclopentyloxy-6-methyl-pyrimidine and 4-chloro-2-cyclopentyloxy-6-methyl-pyrimidine (94 mg, 0.44 mmol) were added and the reaction was heated to 200° C. for 30 minutes in a microwave oven. The solvent was evaporated under reduced pressure and the residue was taken up in water and extracted twice with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate, filtered and evaporated under reduced pressure to dryness. The residue was purified by column chromatography on silica gel using methylenechloride/methanol (19:1 v/v) as eluent to yield the title compound as a white solid (56 mg, 37%). MS ISP (m/e): 380.1 (100) [(M+H)+]. 1H NMR (CDCl3, 300 MHz): δ (ppm)=7.70 (s, 1H), 7.62 (s, 1H), 7.15 (d, 1H), 7.07 (d, 1H), 7.05 (s, 1H), 6.87 (s, 1H), 6.06 (s, 1H), 5.30 (m, 1H), 3.85 (s, 3H), 2.33 (s, 3H), 2.30 (s, 3H), 1.75-2.00 (m, 6H), 1.60-1.68 (m, 2H).

Workup

  1. additionwere added
  2. customThe solvent was evaporated under reduced pressure
  3. extractionextracted twice with ethyl acetate
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. customevaporated under reduced pressure to dryness
  8. customThe residue was purified by column chromatography on silica gel

Sources & evidence

ORD record
ord-05a656810a1246b2b69d4a078827759a
Source dataset
uspto-grants-2015_02
Patent number
US08962834B2

Reaction notes

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