Sodium Hydroxide → 2-(4-(1-((2-aminoethoxy)methyl)-6H-imidazo[1,5-a]pyrrolo[2,3-e]pyrazin-3-yl)phenyl)propan-2-ol

HRID 1628073Notes

Reaction equation

[OH:1][C:2]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[N:12]=[C:13]([CH2:33][O:34][CH2:35][CH2:36][NH:37]C(=O)OCC3C4C=CC=CC=4C4C3=CC=CC=4)[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].[OH-].[Na+]>O1CCOCC1>[NH2:37][CH2:36][CH2:35][O:34][CH2:33][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:7]=[CH:6][C:5]([C:2]([OH:1])([CH3:3])[CH3:4])=[CH:10][CH:9]=2)[N:12]=1

Participants

Conditions

Temperature: 70 °C

Procedure

To a solution of (9H-fluoren-9-yl)methyl 2-((3-(4-(2-hydroxypropan-2-yl)phenyl)-6-tosyl-6H-imidazo[1,5-a]pyrrolo[2,3-e]pyrazin-1-yl)methoxy)ethylcarbamate (0.030 g, 0.040 mmol, Preparation #AW.1) in 1,4-dioxane (1 mL) was added NaOH (5.0 N aqueous, 0.040 mL, 0.20 mmol). The mixture was heated at about 70° C. for about 4 h. The mixture was then concentrated under reduced pressure, dissolved in MeOH/DMSO (1:1) (2 mL) and purified via reverse phase preparatory HPLC (Table 2, Method n). The desired fractions were collected and concentrated under reduced pressure. The residue was dissolved in water (4 mL) and lyophilized for 16 h to give 2-(4-(1-((2-aminoethoxy)methyl)-6H-imidazo[1,5-a]pyrrolo[2,3-e]pyrazin-3-yl)phenyl)propan-2-ol (6.5 mg, 44%): LC/MS (Table 2, Method a) Rt=1.30 min.; MS m/z: 364 (M−H)−.

Workup

concentrationThe mixture was then concentrated under reduced pressure
dissolutiondissolved in MeOH/DMSO (1:1) (2 mL)
custompurified via reverse phase preparatory HPLC (Table 2, Method n)
customThe desired fractions were collected
concentrationconcentrated under reduced pressure
dissolutionThe residue was dissolved in water (4 mL)

Sources & evidence

ORD record: ord-33071ba923684ff396dde1015ef24622
Source dataset: uspto-grants-2014_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08785639B2

Reaction notes

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