Potassium Phosphate, Tribasic → HCID 68680476, compound

HRID 1865470Notes

Reaction equation

HRID 1865470 reaction equation
Cl[C:2]1[N:28]=[C:27]([C:29]([F:32])([F:31])[F:30])[CH:26]=[CH:25][C:3]=1[C:4]([NH:6][CH2:7][C:8]1([CH2:21][CH:22]2[CH2:24][CH2:23]2)[CH2:13][CH2:12][CH:11]([S:14]([CH2:17][CH:18]2[CH2:20][CH2:19]2)(=[O:16])=[O:15])[CH2:10][CH2:9]1)=[O:5].[CH:33]1(B(O)O)[CH2:35][CH2:34]1.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C1(C)C=CC=CC=1.ClCCl.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH:33]1([C:2]2[N:28]=[C:27]([C:29]([F:32])([F:31])[F:30])[CH:26]=[CH:25][C:3]=2[C:4]([NH:6][CH2:7][C:8]2([CH2:21][CH:22]3[CH2:24][CH2:23]3)[CH2:13][CH2:12][CH:11]([S:14]([CH2:17][CH:18]3[CH2:20][CH2:19]3)(=[O:16])=[O:15])[CH2:10][CH2:9]2)=[O:5])[CH2:35][CH2:34]1

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 75806Tricyclohexylphosphine2×HCID 2760897Cyclopropylboronic acidHCID 86609534HCID 86609534, compound

Product 1

HCID 68680476HCID 68680476, compoundYield 30.1%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalyst2×HCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
100 °C

Procedure

2-Chloro-N-(4-cyclopropylmethanesulfonyl-1-cyclopropylmethylcyclohexylmethyl)-6-trifluoromethylnicotinamide (50 mg, 0.10 mmol), cyclopropylboronic acid (44 mg, 0.51 mmol), tricyclohexylphosphine (5.7 mg, 0.02 mmol) and potassium phosphate (75 mg, 0.35 mmol) were dissolved in toluene (1 ml) and water (0.05 ml) and degassed with nitrogen for 5 minutes. Palladium acetate (2.3 mg, 0.01 mmol) was added and the mixture was heated at 100° C. for 5 hours. Palladium acetate (2.3 mg, 0.01 mmol) and tricyclohexylphosphine (5.7 mg, 0.02 mmol) were added and the reaction heated for a further 3 hours. The crude reaction mixture was diluted with dichloromethane (3 ml) and passed through a Phenomonex abw cartrige. The compound was eluted with dichloromethane (10 ml) and the filtrate was evaporated. The residue was purified by preparative plate chromatography on silica eluting with 10% ethyl acetate in dichloromethane. Collecting the appropriate band, trituration of the silica with ethyl acetate, filtration and evaporation gave a colourless oil (15 mg, 30%). 1H NMR δ (ppm)(CDCl3): 7.79 (1H, d, J=7.8 Hz), 7.43 (1H, d, J=7.8 Hz), 6.00 (1H, s), 3.64 (2H, d, J=6.3 Hz), 2.97-2.89 (3H, m), 2.38-2.32 (1H, m), 2.07-1.86 (6H, m), 1.43-1.36 (2H, m), 1.28-1.14 (5H, m), 1.07-1.05 (2H, m), 0.78-0.68 (3H, m), 0.52 (2H, q, J=5.9 Hz), 0.42 (2H, q, J=5.3 Hz), 0.05 (2H, dd, J=0.0, 4.8 Hz). MS (m/e)=499.

Workup

  1. customwater (0.05 ml) and degassed with nitrogen for 5 minutes
  2. temperaturethe reaction heated for a further 3 hours
  3. customThe crude reaction mixture
  4. washThe compound was eluted with dichloromethane (10 ml)
  5. customthe filtrate was evaporated
  6. customThe residue was purified by preparative plate chromatography on silica eluting with 10% ethyl acetate in dichloromethane
  7. customCollecting the appropriate band, trituration of the silica
  8. filtrationwith ethyl acetate, filtration and evaporation

Sources & evidence

ORD record
ord-cbcde757b6ec497792ead6ef658b8371
Source dataset
uspto-grants-2009_12
Patent number
US07626056B2

Reaction notes

Loading…