Trifluoroacetic acid → HCID 86656421, compound

HRID 1628071Notes

Reaction equation

HRID 1628071 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:37](COCC[Si](C)(C)C)[C:16]2[N:17]=[CH:18][C:19]3[N:20]([C:21]([C@@H:24]4[CH2:28][CH2:27][C@H:26]([NH:29]C(=O)OC(C)(C)C)[CH2:25]4)=[N:22][CH:23]=3)[C:15]=2[CH:14]=1.[C:46]([OH:52])([C:48](F)(F)F)=[O:47].[NH4+].[OH-]>C(Cl)Cl>[C:46]([OH:52])(=[O:47])[CH3:48].[C:46]([OH:52])(=[O:47])[CH3:48].[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:37][C:16]2[N:17]=[CH:18][C:19]3[N:20]([C:21]([C@@H:24]4[CH2:28][CH2:27][C@H:26]([NH2:29])[CH2:25]4)=[N:22][CH:23]=3)[C:15]=2[CH:14]=1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 14923Ammonium HydroxideHCID 58382443HCID 58382443, compound

Product 1

HCID 86656421HCID 86656421, compoundYield 53.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

tert-Butyl cis-3-(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)cyclopentylcarbamate (0.331 g, 0.524 mmol, prepared using J.1 from Preparation #I.1 with cis-3-(tert-butoxycarbonylamino)cyclopentanecarboxylic acid [Peptech], and L.1 with mercury(II) trifluoroacetate) in DCM (8 mL) was treated with TFA (2.0 mL, 26 mmol) then stirred for about 1.5 h at rt. The solvents were removed under reduced pressure then the material was dissolved in 1,4-dioxane (4 mL) and treated with concentrated aqueous NH4OH (2.5 mL, 24 mmol). The mixture was heated at about 60° C. for about 30 min. The mixture was concentrated under reduced pressure then dissolved in AcOH (1 mL) and DMF (3.5 mL) then the material was purified by preparative reverse phase HPLC (Table 2, Method i) to give cis-3-(7-(5-methoxy-1-methyl-1H-indol-3-yl)-6H-imidazo[1,5-a]pyrrolo[2,3-e]pyrazin-1-yl)cyclopentanamine diacetate (0.145 g, 53%): LC/MS (Table 2, Method a) Rt=1.73 min; MS m/z 401.2 (M+H)+. Syk IC50=A.

Workup

  1. customThe solvents were removed under reduced pressure
  2. dissolutionthe material was dissolved in 1,4-dioxane (4 mL)
  3. temperatureThe mixture was heated at about 60° C. for about 30 min
  4. concentrationThe mixture was concentrated under reduced pressure
  5. dissolutionthen dissolved in AcOH (1 mL)
  6. customDMF (3.5 mL) then the material was purified by preparative reverse phase HPLC (Table 2, Method i)

Sources & evidence

ORD record
ord-31963760787b428e9940309bb06deaf6
Source dataset
uspto-grants-2014_07
Patent number
US08785639B2

Reaction notes

Loading…