Dichloromethane → HCID 58529730, compound

HRID 1972774Notes

Reaction equation

HRID 1972774 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:12]2[CH:17]=[CH:16][N:15]=[C:14]([N:18]3[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][CH2:19]3)[CH:13]=2)[N:5]2[C:10]=1[C:9]([NH2:11])=[N:8][CH:7]=[N:6]2.[CH2:25]([N:32]1[CH:40]=[C:39]2[C:34]([CH:35]=[C:36](B3OC(C)(C)C(C)(C)O3)[CH:37]=[CH:38]2)=[N:33]1)[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.ClCCl.C(=O)([O-])[O-].[Na+].[Na+]>COCCOC>[CH2:25]([N:32]1[CH:40]=[C:39]2[C:34]([CH:35]=[C:36]([C:2]3[CH:3]=[C:4]([C:12]4[CH:17]=[CH:16][N:15]=[C:14]([N:18]5[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][CH2:19]5)[CH:13]=4)[N:5]4[C:10]=3[C:9]([NH2:11])=[N:8][CH:7]=[N:6]4)[CH:37]=[CH:38]2)=[N:33]1)[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=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 58529320HCID 58529320, compound

Product 1

HCID 58529730HCID 58529730, compoundYield 21%

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
80 °C

Procedure

To a stirred solution of 5-bromo-7-[2-(4-methylpiperazin-1-yl)pyridin-4-yl]pyrrolo[2,1-f][1,2,4]triazin-4-amine (60 mg, 0.16 mmol), 2-benzyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2H-indazole (103 mg, 0.31 mmol), and [1,1′-bis(diphenylphosphino)-ferrocene]dichloro palladium(II) complex with dichloromethane (5.6 mg, 0.008 mmol) in degassed DME (1.2 mL) was added aqueous sodium carbonate solution (2 M, 232 □L). The reaction was heated (80° C.) for 17 h and then cooled to rt. The mixture was partitioned between ethyl acetate (25 mL) and H2O (25 mL) and the layers were separated. The organic phase was washed with brine (25 mL), dried (Na2SO4), and concentrated. The crude material was purified by preparative HPLC using a gradient elution from 5% to 35% acetonitrile in water to obtain 17 mg (21%) of the desired product. 1H NMR (300 MHz, DMSO-d6) δ 8.81-8.79 (m, 1 H), 8.58 (s, 1 H), 8.28-8.21 (s, 1 H), 7.98-7.94 (m, 1 H), 7.87-7.81 (m, 1 H), 7.68 (s, 1H), 7.41-7.29 (m, 5 H), 7.24-7.19 (m, 1H), 7.12-7.08 (m, 1 H), 6.97-6.91 (m, 1 H), 5.67 (s, 2 H), 3.58-3.52 (m, 4 H), 2.44-2.37 (m, 4 H), 2.22 (s, 3 H); ES-MS m/z 516.24 [M+H]+, HPLC RT (min) 2.28.

Workup

  1. temperaturecooled to rt
  2. customThe mixture was partitioned between ethyl acetate (25 mL) and H2O (25 mL)
  3. customthe layers were separated
  4. washThe organic phase was washed with brine (25 mL)
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated
  7. customThe crude material was purified by preparative HPLC
  8. washa gradient elution from 5% to 35% acetonitrile in water

Sources & evidence

ORD record
ord-1e3ceffd073f43f1b766d3a2b3f9347a
Source dataset
uspto-grants-2013_04
Patent number
US08431695B2

Reaction notes

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