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

HRID 1514349Notes

Reaction equation

HRID 1514349 reaction equation
Cl[C:2]1[N:7]=[C:6]([NH:8][C:9]2[CH:14]=[CH:13][C:12]([Cl:15])=[CH:11][CH:10]=2)[CH:5]=[C:4]([CH3:16])[N:3]=1.[NH:17]1[C:25]2[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=2)[CH:19]=[N:18]1>C(#N)C>[Cl:15][C:12]1[CH:13]=[CH:14][C:9]([NH:8][C:6]2[CH:5]=[C:4]([CH3:16])[N:3]=[C:2]([N:18]3[CH:19]=[C:20]4[C:25]([CH:24]=[CH:23][CH:22]=[CH:21]4)=[N:17]3)[N:7]=2)=[CH:10][CH:11]=1.[Cl:15][C:12]1[CH:13]=[CH:14][C:9]([NH:8][C:6]2[CH:5]=[C:4]([CH3:16])[N:3]=[C:2]([N:17]3[C:25]4[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=4)[CH:19]=[N:18]3)[N:7]=2)=[CH:10][CH:11]=1

Participants

5

Reactant 2

HCID 92211H-IndazoleHCID 58026187(2-Chloro-6-methyl-pyrimidin-4-yl)-(4-chloro-phenyl)-amine

Product 2

HCID 24764453(4-Chloro-phenyl)-(2-indazol-2-yl-6-methyl-pyrimidin-4-yl)-amineYield 14%HCID 24825861(4-Chloro-phenyl)-(2-indazol-1-yl-6-methyl-pyrimidin-4-yl)-amineYield 5.3%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
160 °C

Procedure

(2-Chloro-6-methyl-pyrimidin-4-yl)-(4-chloro-phenyl)-amine (300 mg, 1.18 mmol) was dissolved in acetonitrile (4 mL), indazole (150 mg, 1.3 mmol) was added and the mixture was heated in a microwave oven at 160° C. for 30 minutes. The solvent was removed in vacuo and the remaining residue was basified with aqueous sodium hydrogencarbonate and extracted with chloroform. The combined organic phases were dried with sodium sulphate, filtrated and evaporated. The crude product was purified by column chromatography with ethyl acetate-hexane as eluent to give (4-chloro-phenyl)-(2-indazol-2-yl-6-methyl-pyrimidin-4-yl)-amine (56 mg, 14%, mp=224.7-226.7° C.) (LC-ESI-HRMS of [M+H]+ shows 336.1019 Da. Calc. 336.101598 Da, dev. 0.9 ppm) as a white solid and (4-chloro-phenyl)-(2-indazol-1-yl-6-methyl-pyrimidin-4-yl)-amine (21 mg, 5.3%, mp=166.7-168.7° C.) (LC-ESI-HRMS of [M+H]+ shows 336.1007 Da. Calc. 336.101598 Da, dev. −2.7 ppm) as a white solid.

Workup

  1. customThe solvent was removed in vacuo
  2. extractionextracted with chloroform
  3. dry with materialThe combined organic phases were dried with sodium sulphate
  4. filtrationfiltrated
  5. customevaporated
  6. customThe crude product was purified by column chromatography with ethyl acetate-hexane as eluent

Sources & evidence

ORD record
ord-31488919fec946ebb872a34974a54076
Source dataset
uspto-grants-2012_07
Patent number
US08222262B2

Reaction notes

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