Ethylenediamine → HCID 58382033, compound

HRID 1628072Notes

Reaction equation

HRID 1628072 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[N:8]([CH3:12])[CH:7]=[C:6]2[C:13]1[N:43](COCC[Si](C)(C)C)[C:16]2[N:17]=[CH:18][C:19]3[N:20]([C:21]([CH2:24][NH:25]C(=O)OCC4C5C=CC=CC=5C5C4=CC=CC=5)=[N:22][CH:23]=3)[C:15]=2[CH:14]=1.CCCC[N+](CCCC)(CCCC)CCCC.[F-].C(N)CN>CN(C=O)C>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[N:8]([CH3:12])[CH:7]=[C:6]2[C:13]1[NH:43][C:16]2[N:17]=[CH:18][C:19]3[N:20]([C:21]([CH2:24][NH2:25])=[N:22][CH:23]=3)[C:15]=2[CH:14]=1

Participants

5

Reactant 3

HCID 3301EthylenediamineHCID 2724141Tetrabutylammonium FluorideHCID 58382214HCID 58382214, compound

Product 1

HCID 58382033HCID 58382033, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
85 °C

Procedure

To a round bottom flask was added (9H-fluoren-9-yl)methyl (7-(5-methoxy-1-methyl-1H-indol-3-yl)-6-((2-(trimethylsilyl)ethoxy)methyl)-6H-imidazo[1,5-a]pyrrolo[2,3-e]pyrazin-1-yl)methylcarbamate (0.300 g, 0.429 mmol, prepared using J.1 from Preparation #I.1 with 2-(((9H-fluoren-9-yl)methoxy)carbonylamino)acetic acid and L.1 with mercury(II) trifluoroacetate), DMF (10 mL), TBAF (1.0 M in THF, 1.72 mL, 1.72 mmol) and ethylenediamine (0.870 mL, 12.9 mmol). The mixture was heated to about 85° C. for about 6 h. The mixture was cooled to rt and concentrated in vacuo. The crude material was purified by flash chromatography (120 g silica gel column, DCM/MeOH 1:0 to 10:1). The solid was purified by reverse phase preparatory HPLC (Table 2, Method e) to give fractions with the title compound. The fractions were combined and concentrated in vacuo until a precipitate formed. The solid was collected by vacuum filtration and then dried under reduced pressure at about 60° C. for about 16 h to give (7-(5-methoxy-1-methyl-1H-indol-3-yl)-6H-imidazo[1,5-a]pyrrolo[2,3-e]pyrazin-1-yl)methanamine (0.021 g, 14%): LC/MS (Table 2, Method a) Rt=1.53 min; MS m/z 347 (M+H)+. Syk IC50=B.

Workup

  1. temperatureThe mixture was cooled to rt
  2. concentrationconcentrated in vacuo
  3. customThe crude material was purified by flash chromatography (120 g silica gel column, DCM/MeOH 1:0 to 10:1)
  4. customThe solid was purified by reverse phase preparatory HPLC (Table 2, Method e)

Sources & evidence

ORD record
ord-de8bd65dbd8541b793d10aa0223d9570
Source dataset
uspto-grants-2014_07
Patent number
US08785639B2

Reaction notes

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