Hydrochloric Acid → HCID 67130028, compound

HRID 1038814Notes

Reaction equation

[CH:1]1([NH:4][C:5]2[C:6]3[O:36][CH:35]=[CH:34][C:7]=3[N:8]=[C:9]([NH:11][C:12]3[CH:20]=[C:19]4[C:15]([C:16]([C:29]([N:31]([CH3:33])[CH3:32])=[O:30])=[N:17][N:18]4COCC[Si](C)(C)C)=[CH:14][CH:13]=3)[N:10]=2)[CH2:3][CH2:2]1.Cl.O1CCOCC1.[NH4+].[OH-]>ClCCCl>[CH:1]1([NH:4][C:5]2[C:6]3[O:36][CH:35]=[CH:34][C:7]=3[N:8]=[C:9]([NH:11][C:12]3[CH:20]=[C:19]4[C:15]([C:16]([C:29]([N:31]([CH3:33])[CH3:32])=[O:30])=[N:17][NH:18]4)=[CH:14][CH:13]=3)[N:10]=2)[CH2:3][CH2:2]1

Participants

Conditions

Temperature: 70 °C

Procedure

In a vial, 6-(4-(cyclopropylamino)furo[3,2-d]pyrimidin-2-ylamino)-N,N-dimethyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazole-3-carboxamide (0.94 g, 0.19 mmol, prepared using E.2 from Preparation #AI.1 with dimethylamine) and an aqueous solution of HCl (6 N, 0.401 mL, 2.41 mmol) in DCE (4 mL) were added. The mixture was heated at about 70° C. for about 15 h. The mixture was concentrated under reduced pressure and 1,4-dioxane (4 mL) and NH4OH (0.956 mL, 7.36 mmol) were added. The mixture was heated at about 75° C. for about 3 h, concentrated under reduced pressure and the residue was suspended in MeOH (1 mL) and filtered. The filtrate was purified by column chromatography eluting with 35 to 85% of 10% MeOH in DCM/DCM (12 g silica gel) to give 6-(4-(cyclopropylamino)furo[3,2-d]pyrimidin-2-ylamino)-N,N-dimethyl-1H-indazole-3-carboxamide (0.029 g, 42%): LC/MS (Table 2 Method c) Rt=1.52 min.; MS m/z: 378 (M+H)+. Syk IC50=A

Workup

additionwere added
temperatureThe mixture was heated at about 75° C. for about 3 h
concentrationconcentrated under reduced pressure
filtrationfiltered
customThe filtrate was purified by column chromatography
washeluting with 35 to 85% of 10% MeOH in DCM/DCM (12 g silica gel)

Sources & evidence

ORD record: ord-627a602eb46240728d72dbe24feb2ba0
Source dataset: uspto-grants-2013_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08551981B2

Reaction notes

Loading…