Sodium Hydroxide → (R)-4-amino-5-(4-phenoxyphenyl)-7-(pyrrolidin-3-yl)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid

Participants

Reaction Conditions

Reaction Steps

To a mixture of (R)-tert-butyl 3-(4-amino-6-cyano-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)pyrrolidine-1-carboxylate (101) (2.0 g, 4.0 mmol) in ethylene glycol/H2O (20 mL/5 mL) was added and NaOH (1.0 g, 25 mmol). The reaction mixture was purged with N2 (2×) before heated at 150° C. overnight. After cooling to r.t., the reaction was diluted with ice-water, neutralized to pH 7 by slow addition of con. HCl. The aqueous layer was washed with DCM, concentrated under vacuum. Part of the residue was purified by preparative HPLC (RP, C18, 10 to 95% acetonitrile in water (0.2% HCOOH)) to give (R)-4-amino-5-(4-phenoxyphenyl)-7-(pyrrolidin-3-yl)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid (127) (60 mg, 4%) as a white solid. LC-MS (ESI): m/z (M+1) 416.0.

Provenance & Evidence