Ammonia → N-(1H-indazol-4-yl)-3-(2-methyl-6-(methylthio)pyrimidin-4-yl)quinoxalin-2-amine

HRID 1621652Notes

Reaction equation

HRID 1621652 reaction equation
[NH:1]1[C:9]2[CH:8]=[CH:7][CH:6]=[C:5]([NH2:10])[C:4]=2[CH:3]=[N:2]1.Cl[C:12]1[C:21]([C:22]2[CH:27]=[C:26]([S:28][CH3:29])[N:25]=[C:24]([CH3:30])[N:23]=2)=[N:20][C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[N:13]=1.C(O)C.N>Cl.CO.C(Cl)Cl>[NH:1]1[C:9]2[C:4](=[C:5]([NH:10][C:12]3[C:21]([C:22]4[CH:27]=[C:26]([S:28][CH3:29])[N:25]=[C:24]([CH3:30])[N:23]=4)=[N:20][C:19]4[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=4)[N:13]=3)[CH:6]=[CH:7][CH:8]=2)[CH:3]=[N:2]1

Participants

8

Reactant 4

HCID 222AmmoniaHCID 702EthanolHCID 413085NoName_3327HCID 866470562-Chloro-3-(2-methyl-6-(methylthio)pyrimidin-4-yl)quinoxaline

Product 1

HCID 66611881N-(1H-indazol-4-yl)-3-(2-methyl-6-(methylthio)pyrimidin-4-yl)quinoxalin-2-amineYield 45.5%

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidCatalystHCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
160 °C

Procedure

A glass microwave reaction vessel was charged with 1H-indazol-4-amine (220 mg, 1.651 mmol, Key Organics Limited/Bionet Research, United Kingdom), 1 drop of concentrated HCl, 2-chloro-3-(2-methyl-6-(methylthio)pyrimidin-4-yl)quinoxaline (250 mg, 0.826 mmol), and ethanol (2 mL). The reaction mixture was stirred and heated in a Emrys Optmizer microwave reactor (Personal Chemistry, Biotage AB, Inc., Upssala, Sweden) at 160° C. for 1 h. The mixture was cooled to room temperature, then neutralized by 2N NH3 in MeOH, diluted with DCM and filtered through a Celite® (diatomaceous earth). The filtrate was concentrated in vacuo. The crude product was purified by chromatography through a Redi-Sep pre-packed silica gel column (40 g), eluting with a gradient of 0% to 10% 2 M NH3MeOH in DCM to give N-(1H-indazol-4-yl)-3-(2-methyl-6-(methylthio)pyrimidin-4-yl)quinoxalin-2-amine (150 mg, 0.375 mmol, 45.5% yield) as an orange solid. 1H NMR (400 MHz, d6-DMSO) δ 13.23 (s, 1H); 12.59 (s, 1H); 8.50 (d, J=7.63 Hz, 1H); 8.42 (s, 1H); 8.31 (s, 1H); 8.03 (d, J=8.22 Hz, 1H); 7.74-7.85 (m, 2H); 7.59 (t, J=7.43 Hz, 1H); 7.41 (t, J=7.92 Hz, 1H); 7.27 (d, J=8.22 Hz, 1H); 2.91 (s, 3H); 2.68 (s, 3H). m/z (ESI, +ve ion) 400 (M+H)+.

Workup

  1. customA glass microwave reaction vessel
  2. temperatureThe mixture was cooled to room temperature
  3. filtrationfiltered through a Celite® (diatomaceous earth)
  4. concentrationThe filtrate was concentrated in vacuo
  5. customThe crude product was purified by chromatography through a Redi-Sep pre-packed silica gel column (40 g)
  6. washeluting with a gradient of 0% to 10% 2 M NH3MeOH in DCM

Sources & evidence

ORD record
ord-22a47b03c3fc41e49dfdb1c7a96be54e
Source dataset
uspto-grants-2014_07
Patent number
US08772480B2

Reaction notes

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