Hydrochloric Acid → HCID 46214654, compound

HRID 2367180Notes

Reaction equation

HRID 2367180 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([C:8]2[CH:16]=[C:15]3[C:11]([C:12]([NH:17]C(=O)C)=[N:13][NH:14]3)=[CH:10][CH:9]=2)[CH:5]=[C:4]([NH2:21])[N:3]=1.Cl>CO>[NH2:17][C:12]1[C:11]2[C:15](=[CH:16][C:8]([C:6]3[N:7]=[C:2]([NH2:1])[N:3]=[C:4]([NH2:21])[CH:5]=3)=[CH:9][CH:10]=2)[NH:14][N:13]=1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 58504377HCID 58504377, compound

Product 1

HCID 46214654HCID 46214654, compoundYield 10%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
60 °C

Procedure

In a 100 mL flask under argon were combined N-[6-(2,6-diamino-4-pyrimidinyl)-1H-indazol-3-yl]acetamide (0.083 g, 0.29 mmol) and HCl (0.28 mL, 9.4 mmol, 12 M) in CH3OH (20 mL). The reaction mixture was stirred at 60° C. for 8 hours and then cooled to room temperature overnight. The mixture was concentrated and the resulting yellow solid was dissolved in water (3 mL). NaOH (1M) was added to the solution until the pH was 12. The precipitated solid was filtered, washed with water, and dried under vacuum at 40° C. The solid (18 mg) was dissolved in hot DMSO (0.5 mL) and sonicated. The resulting precipitate was filtered. Since HPLC showed the material to be only 90% pure, everything was combined (solids and filtrate) and purified on a Gilson RPHPLC (CH3CN/H2O w/0.1% NH4OH) to afford the title compound (7 mg, 10%) as a white solid. LC-MS (ES) m/z=242 [M+H]+. 1H NMR (400 MHz, DMSO-d6): δ 5.37 (s, 2H), 5.93 (s, 2H), 6.25 (s, 1H), 6.31 (s, 2H), 7.40 (dd, J=8.3, 1.3 Hz, 1H), 7.69 (d, J=8.3 Hz, 1H), 7.82 (s, 1H), 11.51 (s, 1H).

Workup

  1. customIn a 100 mL flask under argon were combined
  2. temperaturecooled to room temperature overnight
  3. concentrationThe mixture was concentrated
  4. dissolutionthe resulting yellow solid was dissolved in water (3 mL)
  5. additionNaOH (1M) was added to the solution until the pH was 12
  6. filtrationThe precipitated solid was filtered
  7. washwashed with water
  8. customdried under vacuum at 40° C
  9. dissolutionThe solid (18 mg) was dissolved in hot DMSO (0.5 mL)
  10. customsonicated
  11. filtrationThe resulting precipitate was filtered
  12. custompurified on a Gilson RPHPLC (CH3CN/H2O w/0.1% NH4OH)

Sources & evidence

ORD record
ord-be3d7b02260649dab359979e1f8e89cb
Source dataset
uspto-grants-2014_04
Patent number
US08697685B2

Reaction notes

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