NoName_3327 → N-(3-(2-methyl-6-(methylthio)pyrimidin-4-yl)pyrazin-2-yl)-1H-indazol-4-amine

HRID 1621493Notes

Reaction equation

HRID 1621493 reaction equation
Cl[C:2]1[C:3]([C:8]2[CH:13]=[C:12]([S:14][CH3:15])[N:11]=[C:10]([CH3:16])[N:9]=2)=[N:4][CH:5]=[CH:6][N:7]=1.[NH:17]1[C:25]2[CH:24]=[CH:23][CH:22]=[C:21]([NH2:26])[C:20]=2[CH:19]=[N:18]1>C(O)C.C([O-])(O)=O.[Na+]>[CH3:16][C:10]1[N:9]=[C:8]([C:3]2[C:2]([NH:26][C:21]3[C:20]4[CH:19]=[N:18][NH:17][C:25]=4[CH:24]=[CH:23][CH:22]=3)=[N:7][CH:6]=[CH:5][N:4]=2)[CH:13]=[C:12]([S:14][CH3:15])[N:11]=1

Participants

5

Reactant 2

HCID 413085NoName_3327HCID 866470514-(3-Chloropyrazin-2-yl)-2-methyl-6-(methylthio)pyrimidine

Product 1

HCID 66612118N-(3-(2-methyl-6-(methylthio)pyrimidin-4-yl)pyrazin-2-yl)-1H-indazol-4-amineYield 46%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
160 °C

Procedure

A glass microwave reaction vessel was charged with 4-(3-chloropyrazin-2-yl)-2-methyl-6-(methylthio)pyrimidine (60 mg, 0.237 mmol) and 1H-indazol-4-amine (63.2 mg, 0.475 mmol, Bionet) in ethanol (2 mL). The reaction mixture was stirred and heated in an Emrys Optmizer microwave reactor (Personal Chemistry, Biotage AB, Inc., Upssala, Sweden) at 160° C. for 30 min. The reaction mixture was diluted with saturated NaHCO3 (5 mL) and extracted with EtOAc (2×30 mL). The combined organic extracts were washed with saturated NaCl (5 mL) and dried over Na2SO4. The solution was filtered and concentrated in vacuo to give a yellow solid. The crude material was adsorbed onto a plug of silica gel and purified by chromatography through a silica gel column eluting with 40% EtOAc/hexanes to provide N-(3-(2-methyl-6-(methylthio)pyrimidin-4-yl)pyrazin-2-yl)-1H-indazol-4-amine (38 mg, 46% yield) as yellow solid. 1H NMR (300 MHz, d8-dioxane) δ 12.49 (s, 1H); 11.68 (s, 1H); 10.69 (s, 1H); 8.24 (s, 2H); 8.10 (d, J=7.60 Hz, 1H); 8.02 (s, 1H); 7.23 (t, J=7.97 Hz, 1H); 7.07 (d, J=8.18 Hz, 1H); 2.83 (s, 3H); 2.53 (s, 3H). m/z (ESI, +ve ion) 350 (M+H)+.

Workup

  1. customA glass microwave reaction vessel
  2. extractionextracted with EtOAc (2×30 mL)
  3. washThe combined organic extracts were washed with saturated NaCl (5 mL)
  4. dry with materialdried over Na2SO4
  5. filtrationThe solution was filtered
  6. concentrationconcentrated in vacuo
  7. customto give a yellow solid
  8. custompurified by chromatography through a silica gel column
  9. washeluting with 40% EtOAc/hexanes

Sources & evidence

ORD record
ord-be7fb589913445a5897294bad7190f33
Source dataset
uspto-grants-2014_07
Patent number
US08772480B2

Reaction notes

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