Methyl Benzoate → HCID 11327913, compound

HRID 2056012Notes

Reaction equation

HRID 2056012 reaction equation
C([Mg]Cl)(C)C.C1COCC1.Br[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][N:13]=1.C(OC)(=O)C1C=CC=CC=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2)CCCCC1.[CH3:53][O:54][C:55]([C:57]1([NH:61][C:62]([C:64]2[CH:72]=[C:71]3[C:67]([C:68]([CH:75]4[CH2:79][CH2:78][CH2:77][CH2:76]4)=[C:69](Cl)[N:70]3[CH3:73])=[CH:66][CH:65]=2)=[O:63])[CH2:60][CH2:59][CH2:58]1)=[O:56]>[Zn+2].[Br-].[Br-].C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CN1CCCC1=O>[CH3:53][O:54][C:55]([C:57]1([NH:61][C:62]([C:64]2[CH:72]=[C:71]3[C:67]([C:68]([CH:75]4[CH2:76][CH2:77][CH2:78][CH2:79]4)=[C:69]([C:12]4[CH:17]=[CH:16][CH:15]=[CH:14][N:13]=4)[N:70]3[CH3:73])=[CH:66][CH:65]=2)=[O:63])[CH2:60][CH2:59][CH2:58]1)=[O:56]

Participants

10

Reactant 6

HCID 7150Methyl BenzoateHCID 79732-BromopyridineHCID 8028TetrahydrofuranHCID 27342162-(Dicyclohexylphosphino)biphenylHCID 11531203HCID 11531203, compoundHCID 178418918HCID 178418918, compound

Product 1

HCID 11327913HCID 11327913, compound

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 10421208Zinc bromideCatalystHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
35 °C

Procedure

To a solution of i-PrMgCl in THF (10 mL, 20 mmol) was added 2-bromopyridine (1.93 g, 20.2 mmol) at room temperature in one portion. The mixture was stirred at 35° C. for 0.5 h. To the deep-red solution was added ZnBr2 (4.50 g, 20 mmol) under argon and the resulting mixture was stirred at 70° C. for 0.5 h to obtain a thick white slurry. 1-Methyl-2-pyrrolidinone (20 mL) was added and followed by methyl benzoate (2.5 mL, 20 mmol). The mixture was stirred at 70° C. for 0.5 h. The mixture was cooled to room temperature. Palladium acetate (56.1 mg, 0.25 mmol), 2-dicyclohexylphosphinobiphenyl (350.5 mg, 1 mmol) and 1-[(2-chloro-3-cyclopentyl-1-methyl-1H-indole-6-carbonyl)-amino]-cyclobutanecarboxylic acid methyl ester (1.944 g, 5 mmol) were added. The mixture was stirred at 90° C. until no starting material was left (˜4 h) as monitored by HPLC. The ratio of the coupling product and the starting material was estimated to be 78/22 by HPLC.

Workup

  1. stirringthe resulting mixture was stirred at 70° C. for 0.5 h
  2. customto obtain a thick white slurry
  3. stirringThe mixture was stirred at 70° C. for 0.5 h
  4. temperatureThe mixture was cooled to room temperature
  5. stirringThe mixture was stirred at 90° C. until no starting material
  6. waitwas left (˜4 h)

Sources & evidence

ORD record
ord-e53599639d634f0f98c9c9994eab86ca
Source dataset
uspto-grants-2008_02
Patent number
US07332614B2

Reaction notes

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