Hydrazine → HCID 58382062, compound

HRID 1628119Notes

Reaction equation

HRID 1628119 reaction equation
[OH:1][C:2]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[N:12]=[C:13]([C:33]3[CH:50]=[CH:49][CH:48]=[CH:47][C:34]=3[CH2:35][N:36]3C(=O)C4C(=CC=CC=4)C3=O)[N:14]3[C:19]4[CH:20]=[CH:21][N:22](S(C5C=CC(C)=CC=5)(=O)=O)[C:18]=4[N:17]=[CH:16][C:15]=23)=[CH:7][CH:6]=1)([CH3:4])[CH3:3].NN.[OH-].[Na+]>CCO.CCOC(C)=O>[NH2:36][CH2:35][C:34]1[CH:47]=[CH:48][CH:49]=[CH:50][C:33]=1[C:13]1[N:14]2[C:19]3[CH:20]=[CH:21][NH:22][C:18]=3[N:17]=[CH:16][C:15]2=[C:11]([C:8]2[CH:9]=[CH:10][C:5]([C:2]([OH:1])([CH3:3])[CH3:4])=[CH:6][CH:7]=2)[N:12]=1

Participants

6

Reactant 3

HCID 9321HydrazineHCID 14798Sodium HydroxideHCID 58382221HCID 58382221, compound

Product 1

HCID 58382062HCID 58382062, compoundYield 25%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
85 °C

Procedure

The 2-(2-(3-(4-(2-hydroxypropan-2-yl)phenyl)-6-tosyl-6H-imidazo[1,5-a]pyrrolo[2,3-e]pyrazin-1-yl)benzyl)isoindoline-1,3-dione (0.154 g, 0.226 mmol) in EtOH (4 mL) was treated with hydrazine (0.147 mL, 4.68 mmol) then heated to about 85° C. for about 15 min. The mixture was diluted with EtOAc (20 mL). The insoluble material was removed by filtration and washed with EtOAc (5 mL). The filtrate was concentrated under reduced pressure then the material was dissolved in 1,4-dioxane (4 mL) and treated with aqueous NaOH (50 wt %, 0.260 g, 3.25 mmol). The mixture was heated in a microwave at about 120° C. for about 20 min. The mixture was concentrated under reduced pressure then dissolved in AcOH (1 mL) and DMF (3 mL). The material was purified by preparative reverse phase HPLC (Table 2, Method i). The fractions with desired material were collected and lyophilized. The material was purified using a 5 g Si-Carbonate column (Silicycle™) and eluting wiht MeOH. The material was treated with EtOAc (˜10 mL) then concentrated under reduced pressure. This was repeated several times until a yellow solid was obtained. The material was triturated with EtOAc (3 mL) and heptane (15 mL) and the solid was collected by filtration and dried to constant weight under vacuum at about 70° C. to give 2-(4-(1-(2-(aminomethyl)phenyl)-6H-imidazo[1,5-a]pyrrolo[2,3-e]pyrazin-3-yl)phenyl)propan-2-ol (0.022 g, 25%): LC/MS (Table 2, Method a) Rt=1.62 min; MS m/z 398 (M+H)+. Syk IC50=B.

Workup

  1. customThe insoluble material was removed by filtration
  2. washwashed with EtOAc (5 mL)
  3. concentrationThe filtrate was concentrated under reduced pressure
  4. dissolutionthe material was dissolved in 1,4-dioxane (4 mL)
  5. temperatureThe mixture was heated in a microwave at about 120° C. for about 20 min
  6. concentrationThe mixture was concentrated under reduced pressure
  7. dissolutionthen dissolved in AcOH (1 mL)
  8. customThe material was purified by preparative reverse phase HPLC (Table 2, Method i)
  9. customThe fractions with desired material were collected
  10. customThe material was purified
  11. washeluting wiht MeOH
  12. additionThe material was treated with EtOAc (˜10 mL)
  13. concentrationthen concentrated under reduced pressure
  14. customwas obtained
  15. customThe material was triturated with EtOAc (3 mL) and heptane (15 mL)
  16. filtrationthe solid was collected by filtration
  17. customdried to constant weight under vacuum at about 70° C.

Sources & evidence

ORD record
ord-bd04f165f57749c6b79d468521f504c0
Source dataset
uspto-grants-2014_07
Patent number
US08785639B2

Reaction notes

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