Hydrochloric Acid → 7-(2-Fluoro-4-methylsulfanyl-phenylamino)-pyrrolo[1,2-c]pyrimidine-6-carboxylic acid (2-hydroxy-ethoxy)-amide
Reaction equation
C([O:3][CH2:4][CH2:5][O:6][NH:7][C:8]([C:10]1[CH:11]=[C:12]2[CH:17]=[CH:16][N:15]=[CH:14][N:13]2[C:18]=1[NH:19][C:20]1[CH:25]=[CH:24][C:23]([S:26][CH3:27])=[CH:22][C:21]=1[F:28])=[O:9])=C.Cl>>[OH:3][CH2:4][CH2:5][O:6][NH:7][C:8]([C:10]1[CH:11]=[C:12]2[CH:17]=[CH:16][N:15]=[CH:14][N:13]2[C:18]=1[NH:19][C:20]1[CH:25]=[CH:24][C:23]([S:26][CH3:27])=[CH:22][C:21]=1[F:28])=[O:9]Participants
3
Procedure
To a solution of 7-(2-fluoro-4-methylsulfanyl-phenylamino)-pyrrolo[1,2-c]pyrimidine-6-carboxylic acid (2-vinyloxy-ethoxy)-amide in IMS was added aqueous hydrochloric acid (4 N, 0.5 mL). The reaction was stirred at room temperature for 1 hour then concentrated in vacuo. The resultant residue was dissolved in ethyl acetate (5 mL), washed with aqueous saturated sodium bicarbonate solution (10 mL) and the aqueous fraction extracted twice with ethyl acetate (2×5 mL). The combined organic fractions were washed with brine, dried (MgSO4) and concentrated in vacuo. The resultant residue was subjected to flash chromatography (SiO2, gradient 0-10% DCM in methanol) to yield the title compound as an off-white solid (73 mg, 56%). 1H NMR (DMSO-d6): 11.31 (1H, s), 8.65 (1H, s), 7.85 (1H, s), 7.42-7.37 (2H, m), 7.15 (1H, dd, J=12.10, 2.09 Hz), 6.82-6.79 (1H, m), 6.73 (1H, s), 6.06 (1H, t, J=8.82 Hz), 4.66 (1H, s), 3.75 (2H, dd, J=5.34, 4.47 Hz), 3.46 (2H, t, J=4.82 Hz), 2.36 (3H, s). LCMS (Method A): RT=7.35 min, M+H+=377.