Boron Trichloride → HCID 178429230, compound

HRID 734756Notes

Reaction equation

HRID 734756 reaction equation
[Br:1][C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([NH:11][C:12]([C:14]3[CH:19]([C:20]4[CH:25]=[CH:24][C:23]([Cl:26])=[C:22]([O:27]C)[CH:21]=4)[CH2:18][C:17](=[O:29])[NH:16][C:15]=3[CH3:30])=[O:13])[CH:9]=2)[NH:4][N:3]=1.B(Cl)(Cl)Cl>C(Cl)Cl.CCOC(C)=O.O.[OH-].[Na+]>[Br:1][C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([NH:11][C:12]([C:14]3[CH:19]([C:20]4[CH:25]=[CH:24][C:23]([Cl:26])=[C:22]([OH:27])[CH:21]=4)[CH2:18][C:17](=[O:29])[NH:16][C:15]=3[CH3:30])=[O:13])[CH:9]=2)[NH:4][N:3]=1

Participants

7

Reactant 2

HCID 25135Boron Trichloride2×HCID 178487580N-(3-Bromo-1H-indazol-5-yl)-4-[4-chloro-3-(methyloxy)phenyl]-2-methyl-6-oxo-1,4,5,6-tetrahydro-3-pyridinecarboxamide

Product 1

HCID 178429230HCID 178429230, compoundYield 27.7%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolventHCID 14798Sodium HydroxideSolvent

Conditions

Temperature
35 °C

Procedure

The product from Example 94 (95 mg, 0.19 mmol, 1.0 equiv) was cooled to −78° C. in 2.0 mL CH2Cl2 and BCl3 (1.0 M in CH2Cl2, 2.90 mL, 2.91 mmol, 15.0 equiv) was added dropwise. The reaction was warmed to 35° C. and stirred for 90 hours. An additional portion of BCl3 (2.90 mL, 2.91 mmol, 15.0 equiv) was added dropwise and the reaction was stirred for another 96 hours. The reaction mixture was diluted with EtOAc and water and basified to pH 14 with 6N NaOH. The phases were separated, and the aqueous phase was acidified to pH 4 with 6N HCl. The precipitate was filtered and washed with Et2O. The residue was purified by reverse-phase HPLC (10-95% CH3CN/H2O, 0.1% TFA over 18 minutes, retention time 10.63 min) to provide 25 mg (27%) of the title compound as a white solid. MS (ES+) m/e 476 [M+H]+

Workup

  1. stirringthe reaction was stirred for another 96 hours
  2. customThe phases were separated
  3. filtrationThe precipitate was filtered
  4. washwashed with Et2O
  5. customThe residue was purified by reverse-phase HPLC (10-95% CH3CN/H2O, 0.1% TFA over 18 minutes, retention time 10.63 min)

Sources & evidence

ORD record
ord-0ccb5ce629d34335952ec46ab59abaaa
Source dataset
uspto-grants-2009_09
Patent number
US07592357B2

Reaction notes

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