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

HRID 1812064Notes

Reaction equation

HRID 1812064 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 887MethanolSolvent2×HCID 6344DichloromethaneSolvent2×

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 (250mg, 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 2 N NH3 in MeOH, diluted with DCM and filterd 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% to10% 2 M NH3.MeOH 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. concentrationThe filtrate was concentrated in vacuo
  4. customThe crude product was purified by chromatography through a Redi-Sep pre-packed silica gel column (40 g)
  5. washeluting with a gradient of 0% to10% 2 M NH3

Sources & evidence

ORD record
ord-b33a2f925a494defb4714b33316e91ce
Source dataset
uspto-grants-2013_01
Patent number
US08362241B2

Reaction notes

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