4-Methylmorpholine → 1h-Pyrrolo[2,3-c]pyridine-5-carboxamide,1-[(2,4-difluorophenyl)methyl]-n-hydroxy-3-[(2-methoxyethoxy)methyl]-n-methyl-

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Reaction Conditions

Reaction Steps

To a solution of 1-(2,4-difluorobenzyl)-3-[(2-methoxyethoxy)methyl]-1H-pyrrolo[2,3-c]pyridine-5-carboxylic acid 782 mg 2.078 mmol) in anhydrous DMF (10 ml) was added CDMT (438 mg 2.439 mmol 1.2 eq.) and NMM (N-methyl morpholine) (0.28 ml 2.493 mmol 1.2 eq.). The mixture, under nitrogen, was stirred for 2.0 hours, during which it slowly darkened to a deep orange. N-Methylhydroxylamine hydrochloride (868 mg 10.389 mmol 5.0 eq) was added and stirring continued for 10 hours. The reaction was judged to be complete by HPLC-MS analysis and the volatiles were removed in vacuo (ca. 2 torr) to give a golden yellow oil. This oil was dissolved in EtOAc (30 mL) and washed with water (3×20 mL) and brine (20 mL). The organic phase was separated, dried (Na2SO4), and concentrated in vacuo to afford the crude product which was purified by recrystallisation in hot IPA (20 ml) with cooling at 4° C. overnight to give 556 mg (66%) of 1-(2,4-difluorobenzyl)-N-hydroxy-3-[(2-methoxyethoxy)methyl]-N-methyl-1H-pyrrolo[2,3-c]pyridine-5-carboxamide as a pale tan powder. LC-MS (Eclipse XDB-C8, 0.8 mL/min, gradient 80:20 to 5:95H2O (+0.1% HOAc):CH3CN—3 minutes, APCI, +mode): RT—1.08 min, m/e=344.2 (M+H+, base).

Provenance & Evidence