Sodium Carbonate → HCID 67129991, compound

Participants

Reaction Steps

6-(4-(Cyclopropylamino)furo[3,2-d]pyrimidin-2-ylamino)-1H-indazole-3-carboxylic acid (0.13 g, 0.37 mmol, [prepared using I from methyl 6-nitro-1-(2-(trimethylsilyl)ethoxy)methyl)-1H-indazole-3-carboxylate [WO 2010/027500 page 171 intermediate 83 step A], B with Preparation #A.1, J and AI), cyclopropylamine (0.013 mL, 0.18 mmol), and HATU (0.078 g, 0.20 mmol) were combined in DMF (1.9 mL). DIEA (0.081 mL, 0.46 mmol) was added and the mixture was stirred at rt for about 18 h. Additional cyclopropylamine (0.013 mL, 0.19 mmol) was added and the mixture was stirred for about 6 h. HATU (0.04 g, 0.10 mmol) and DIEA (0.1 mL) were added and the mixture was stirred for about 24 h. A solution of 1 M aqueous Na2CO3 (5 mL) was added. The aqueous layer was separated and extracted with DCM (3×10 mL). The combined organic layers were washed with brine (5 mL), dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was dissolved in a mixture of MeOH and DCM and adsorbed onto silica gel (˜3 mL). The residue was purified by column chromatography (25 g silica gel) eluting with 2-8% MeOH in DCM to give N-cyclopropyl-6-(4-(cyclopropylamino)furo[3,2-d]pyrimidin-2-ylamino)-1H-indazole-3-carboxamide (0.052 g, 72%) as a white solid on drying under vacuum at about 40° C.: LCMS (Table 2, Method c) Rt=1.80 min.; MS m/z: 390 (M+H)+. Syk IC50=A

Provenance & Evidence