Dichloromethane → HCID 58529602, compound

HRID 1972961Notes

Reaction equation

HRID 1972961 reaction equation
[NH2:1][C:2]1[C:7]2=[C:8](Br)[CH:9]=[C:10]([CH:11]([OH:14])[CH2:12][CH3:13])[N:6]2[N:5]=[CH:4][N:3]=1.[CH2:16]([N:23]1[CH:31]=[C:30]2[C:25]([CH:26]=[C:27](B3OC(C)(C)C(C)(C)O3)[CH:28]=[CH:29]2)=[N:24]1)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.ClCCl.C(=O)([O-])[O-].[Na+].[Na+]>CCO.C1(C)C=CC=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[NH2:1][C:2]1[C:7]2=[C:8]([C:27]3[CH:28]=[CH:29][C:30]4[C:25]([CH:26]=3)=[N:24][N:23]([CH2:16][C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[CH:31]=4)[CH:9]=[C:10]([CH:11]([OH:14])[CH2:12][CH3:13])[N:6]2[N:5]=[CH:4][N:3]=1

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 585293132-benzyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2H-IndazoleHCID 58529650HCID 58529650, compound

Product 1

HCID 58529602HCID 58529602, compoundYield 57%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 21863594Toluene ethanolSolvent

Conditions

Temperature
80 °C

Procedure

1-(4-Amino-5-bromo-pyrrolo[2,1-f][1,2,4]triazin-7-yl)-propan-1-ol (355 mg, 1.31 mmol) and 2-benzyl-6-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-2H-indazole (656.4 mg, 1.96 mmol, 1.5 eq) were dissolved in 1:1 EtOH-toluene (11 mL each) and degassed with nitrogen. After 30 minutes [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium (II) complexed with dichloromethane (95.8 mg, 0.13 mmol, 0.1 eq) followed by 2M sodium carbonate solution (1.31 mL, 2.62 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 rid of excess palladium salts. The organic layer was washed with water and brine, dried over Na2SO4, 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 295.3 mg (57%) of the title compound as beige solid. 1H NMR (300 MHz, DMSO-d6) δ 8.54 (s, 1 H), 7.88 (s, 1 H), 7.80 (d, 1 H), 7.57 (s, 1 H), 7.34-7.28 (m, 5 H), 7.13 (dd, 1 H), 6.66 (s, 1 H), 5.65 (s, 2 H), 5.23 (d, 1H), 5.04 to 4.99 (m, 1H), 1.89 to 1.83 (m, 1H), 1.78 to 1.70 (m, 1H), 0.90 (t, 3H); ES-MS m/z 399.3 [M+H]+, RT (min) 2.55.

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. washThe organic layer was washed with water and brine
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe crude product was purified
  11. additionthe product containing fractions
  12. concentrationwere concentrated

Sources & evidence

ORD record
ord-ba22c10f151545ad887b8aabac381a7b
Source dataset
uspto-grants-2013_04
Patent number
US08431695B2

Reaction notes

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