Hydrochloric Acid → N-(3-(2-methyl-9H-purin-6-yl)pyridin-4-yl)-1H-indazol-4-amine

HRID 1621490Notes

Reaction equation

HRID 1621490 reaction equation
Cl[C:2]1[CH:7]=[CH:6][N:5]=[CH:4][C:3]=1[C:8]1[N:16]=[C:15]([CH3:17])[N:14]=[C:13]2[C:9]=1[N:10]=[CH:11][N:12]2C1CCCCO1.[NH:24]1[C:32]2[CH:31]=[CH:30][CH:29]=[C:28]([NH2:33])[C:27]=2[CH:26]=[N:25]1.Cl>C(O)C.C([O-])(O)=O.[Na+]>[CH3:17][C:15]1[N:14]=[C:13]2[C:9]([N:10]=[CH:11][NH:12]2)=[C:8]([C:3]2[CH:4]=[N:5][CH:6]=[CH:7][C:2]=2[NH:33][C:28]2[C:27]3[CH:26]=[N:25][NH:24][C:32]=3[CH:31]=[CH:30][CH:29]=2)[N:16]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 413085NoName_3327HCID 666000086-(4-chloropyridin-3-yl)-2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purine

Product 1

HCID 178432622N-(3-(2-methyl-9H-purin-6-yl)pyridin-4-yl)-1H-indazol-4-amineYield 67.2%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
160 °C

Procedure

A glass microwave reaction vessel was charged with 6-(4-chloropyridin-3-yl)-2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purine (33 mg, 0.100 mmol) and 1H-indazol-4-amine (26.6 mg, 0.200 mmol, Bionet Research, Cornwall, UK) in Ethanol (1 mL) and a drop of 5 N HCl. The reaction mixture was stirred and heated in a 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 (3 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 10% MeOH/CH2Cl2 to provide N-(3-(2-methyl-9H-purin-6-yl)pyridin-4-yl)-1H-indazol-4-amine (23 mg, 67% yield) as yellow solid. 1H NMR (300 MHz, d6-DMSO) δ 13.27 (s, 1H); 12.54 (s, 1H); 10.22 (s, 1H); 8.64 (s, 1H); 8.30 (d, J=5.85 Hz, 1H); 8.16 (s, 1H); 7.30-7.43 (m, 3H); 7.18 (d, J=6.87 Hz, 1H); 2.82 (s, 3H). m/z (ESI, +ve ion) 343 (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 (3 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 10% MeOH/CH2Cl2

Sources & evidence

ORD record
ord-2519315fc4a74961b4b6aceebfa41328
Source dataset
uspto-grants-2014_07
Patent number
US08772480B2

Reaction notes

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