Dichloromethane → HCID 58529599, compound

HRID 1972965Notes

Reaction equation

HRID 1972965 reaction equation
[NH2:1][C:2]1[C:7]2=[C:8](Br)[CH:9]=[C:10]([CH2:11][CH2:12][OH:13])[N:6]2[N:5]=[CH:4][N:3]=1.[CH2:15]([N:22]1[CH:30]=[C:29]2[C:24]([CH:25]=[C:26](B3OC(C)(C)C(C)(C)O3)[CH:27]=[CH:28]2)=[N:23]1)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.ClCCl.C(=O)([O-])[O-].[Na+].[Na+]>CCO.C1(C)C=CC=CC=1>[NH2:1][C:2]1[C:7]2=[C:8]([C:26]3[CH:27]=[CH:28][C:29]4[C:24]([CH:25]=3)=[N:23][N:22]([CH2:15][C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[CH:30]=4)[CH:9]=[C:10]([CH2:11][CH2:12][OH:13])[N:6]2[N:5]=[CH:4][N:3]=1

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 585293132-benzyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2H-IndazoleHCID 59232026HCID 59232026, compound

Product 1

HCID 58529599HCID 58529599, compoundYield 36.6%

Reagents, catalysts & solvents 1

HCID 21863594Toluene ethanolSolvent

Conditions

Temperature
80 °C

Procedure

2-(4-Amino-5-bromo-pyrrolo[2,1-f][1,2,4]triazin-7-yl)-ethanol (425 mg, 1.65 mmol) and 2-benzyl-6-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-2H-indazole (828.8 mg, 2.48 mmol, 1.5 eq) were dissolved in 1:1 EtOH-toluene (33 mL each) and degassed with nitrogen. After 30 minutes, [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium (II) complexed with dichloromethane (121 mg, 0.17 mmol, 0.1 eq) followed by 2M aqueous sodium carbonate solution (1.65 mL, 3.31 mmol, 2.0 eq) were added. The reaction mixture was stirred at 80° C. for 17 h and cooled to rt. The reaction mixture was partitioned between EtOAc and water and filtered through a pad of Celite® to remove excess palladium salts. The organic layer was washed with water and brine, dried over Mg2SO4, filtered, and concentrated in vacuo. The crude product was purified using an ISCO® instrument (gradient 1 to 100% [20% MeOH/DCM+1% Et3N]/DCM) and the product containing fractions were concentrated. Trituration with DCM-hexane gave 232.3 mg (36%) of the title compound as beige solid. 1H NMR (300 MHz, DMSO-d6) δ 8.54 (s, 1H), 7.88 (s, 1H), 7.79 (d, 1H), 7.56 (s, 1H), 7.34-7.28 (m, 5H), 7.13 (dd, 1H), 6.62 (s, 1H), 5.64 (s, 2H), 4.76 (t, 1H), 3.72 (q, 2H), 3.04 (t, 2H); ES-MS m/z 385.2 [M+H]+, RT (min) 2.25.

Workup

  1. customdegassed with nitrogen
  2. additionwere added
  3. temperaturecooled to rt
  4. customThe reaction mixture was partitioned between EtOAc and water
  5. filtrationfiltered through a pad of Celite®
  6. customto remove excess palladium salts
  7. washThe organic layer was washed with water and brine
  8. dry with materialdried over Mg2SO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe crude product was purified
  12. additionthe product containing fractions
  13. concentrationwere concentrated

Sources & evidence

ORD record
ord-1d34f81db69948ae8e38a6134144b89d
Source dataset
uspto-grants-2013_04
Patent number
US08431695B2

Reaction notes

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