Nitrogen → HCID 67527663, compound

HRID 2261867Notes

Reaction equation

HRID 2261867 reaction equation
[CH2:1]([O:3][C:4](=[O:24])[CH2:5][C:6]1[C:7]2[CH:14]=[CH:13][C:12](B3OC(C)(C)C(C)(C)O3)=[CH:11][C:8]=2[S:9][CH:10]=1)[CH3:2].Br[C:26]1[CH:49]=[CH:48][C:29]([O:30][CH2:31][C:32]2[N:36]([C:37]3[C:42]([Cl:43])=[CH:41][CH:40]=[CH:39][C:38]=3[Cl:44])[N:35]=[CH:34][C:33]=2[CH:45]([CH3:47])[CH3:46])=[CH:28][C:27]=1[CH3:50].N#N.C1(P(C2CCCCC2)C2(OC)CC=CC(OC)=C2C2C=CC=CC=2)CCCCC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C1(C)C=CC=CC=1.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH2:1]([O:3][C:4](=[O:24])[CH2:5][C:6]1[C:7]2[CH:14]=[CH:13][C:12]([C:26]3[CH:49]=[CH:48][C:29]([O:30][CH2:31][C:32]4[N:36]([C:37]5[C:42]([Cl:43])=[CH:41][CH:40]=[CH:39][C:38]=5[Cl:44])[N:35]=[CH:34][C:33]=4[CH:45]([CH3:46])[CH3:47])=[CH:28][C:27]=3[CH3:50])=[CH:11][C:8]=2[S:9][CH:10]=1)[CH3:2]

Participants

8

Reactant 5

HCID 947NitrogenHCID 62657Potassium Phosphate, TribasicHCID 665453372-Dicyclohexylphosphino-2,6-dimethoxybiphenylHCID 67272278[6-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzo[b]thiophen-3-yl]-acetic acid ethyl esterHCID 675277775-(4-Bromo-3-methyl-phenoxymethyl)-1-(2,6-dichloro-phenyl)-4-isopropyl-1H-pyrazole

Product 1

HCID 67527663HCID 67527663, compoundYield 12%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

A solution of [6-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzo[b]thiophen-3-yl]-acetic acid ethyl ester (267 mg, 0.770 mmol) and 5-(4-bromo-3-methyl-phenoxymethyl)-1-(2,6-dichloro-phenyl)-4-isopropyl-1H-pyrazole (280 mg, 0.616 mmol) in toluene (10 mL) is evacuated and refilled with N2 three times. Pd(OAc)2 (5.5 mg, 0.024 mmol), 2-dicyclohexylphosphino-2,6-dimethoxy-1,1′-biphenyl (20 mg, 0.049 mmol), and potassium phosphate, tribasic, N-hydrate (262 mg, 1.23 mmol) are added. The mixture is stirred at 100° C. for 15 hours. The reaction mixture is cooled to room temperature and filtered through a pad of celite. The filtrate is concentrated, and the residue is purified by flash chromatography (eluted with 25% EtOAc/Hexanes) and the appropriate fractions are concentrated. The material is dried in vacuo to afford (6-{4-[2-(2,6-dichloro-phenyl)-4-isopropyl-2H-pyrazol-3-ylmethoxy]-2-methyl-phenyl}-benzo[b]thiophen-3-yl)-acetic acid ethyl ester (43 mg, 12% yield). ES/MS m/e 592.8; 594.8 (M+1).

Workup

  1. temperatureThe reaction mixture is cooled to room temperature
  2. filtrationfiltered through a pad of celite
  3. concentrationThe filtrate is concentrated
  4. customthe residue is purified by flash chromatography (eluted with 25% EtOAc/Hexanes)
  5. concentrationthe appropriate fractions are concentrated
  6. customThe material is dried in vacuo

Sources & evidence

ORD record
ord-c832938346ff4daba67c83173b3cb773
Source dataset
uspto-grants-2010_12
Patent number
US07846960B2

Reaction notes

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