1H-Indazole → (4-Chloro-phenyl)-(6-indazol-2-yl-pyrazin-2-yl)-amine

HRID 1514361Notes

Reaction equation

HRID 1514361 reaction equation
[H-].[Na+].[NH:3]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH:5]=[N:4]1.[Cl:12][C:13]1[CH:18]=[CH:17][C:16]([N:19]([C:26]2[CH:31]=[N:30][CH:29]=[C:28](Cl)[N:27]=2)C(=O)C(C)(C)C)=[CH:15][CH:14]=1>CN(C)C=O>[Cl:12][C:13]1[CH:14]=[CH:15][C:16]([NH:19][C:26]2[CH:31]=[N:30][CH:29]=[C:28]([N:4]3[CH:5]=[C:6]4[C:11]([CH:10]=[CH:9][CH:8]=[CH:7]4)=[N:3]3)[N:27]=2)=[CH:17][CH:18]=1.[Cl:12][C:13]1[CH:14]=[CH:15][C:16]([NH:19][C:26]2[CH:31]=[N:30][CH:29]=[C:28]([N:3]3[C:11]4[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=4)[CH:5]=[N:4]3)[N:27]=2)=[CH:17][CH:18]=1

Participants

6

Reactant 3

HCID 92211H-IndazoleHCID 24758Sodium hydrideHCID 58026185N-(4-Chloro-phenyl)-N-(6-chloro-pyrazin-2-yl)-2,2-dimethyl-propionamide

Product 2

HCID 24826048(4-Chloro-phenyl)-(6-indazol-2-yl-pyrazin-2-yl)-amineYield 13%HCID 24826049(4-Chloro-phenyl)-(6-indazol-1-yl-pyrazin-2-yl)-amineYield 12%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

Sodium hydride (180 mg, 4.50 mmol) was added to a suspension of indazole (543 mg, 4.40 mmol) in N,N-dimethylformamide (5 mL) and the reaction mixture was stirred at 50° C. for 20 minutes. To this suspension N-(4-chloro-phenyl)-N-(6-chloro-pyrazin-2-yl)-2,2-dimethyl-propionamide (300 mg, 0.88 mmol) was added and stirred at 100° C. over night. The reaction mixture was quenched with brine and extracted with ethyl acetate (4×15 mL). The combined organic phases were washed with brine, dried over sodium sulphate, filtrated and evaporated. The crude product was purified by column chromatography with ethyl acetate-heptane as eluent to give (4-chloro-phenyl)-(6-indazol-2-yl-pyrazin-2-yl)-amine (17 mg, 13%, Mp 249-252° C., LC-ESI-HRMS of [M+H]+ shows 322.0864 Da. Calc. 322.085948 Da, dev. 1.4 ppm) as a yellow solid, and (4-chloro-phenyl)-(6-indazol-1-yl-pyrazin-2-yl)-amine (19 mg, 12%, Mp. 204-207° C., LC-ESI-HRMS of [M+H]+ shows 322.0876 Da. Calc. 322.085948 Da, dev. 5.1 ppm) as a brown solid.

Workup

  1. stirringstirred at 100° C. over night
  2. customThe reaction mixture was quenched with brine
  3. extractionextracted with ethyl acetate (4×15 mL)
  4. washThe combined organic phases were washed with brine
  5. dry with materialdried over sodium sulphate
  6. filtrationfiltrated
  7. customevaporated
  8. customThe crude product was purified by column chromatography with ethyl acetate-heptane as eluent

Sources & evidence

ORD record
ord-fab18b3e04f045809e6f49d1663f2644
Source dataset
uspto-grants-2012_07
Patent number
US08222262B2

Reaction notes

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