Ammonium Hydroxide → HCID 178491111, compound

Participants

Reaction Conditions

Reaction Steps

To a suspension of 5-chloro-8-fluoro-3-[(4-methylphenyl)sulfonyl]pyrrolo[2′,3′:4,5]pyrimido[6,1-b]quinazolin-7(3H)-one HCl salt (0.5 g, 1.04 mmol) in 2,2,2-trifluoroethanol (10 mL) was added N1-[5-amino-2-methyl-4-(methyloxy)phenyl]-N1,N2,N2-trimethylglycinamide (0.275 g, 1.10 mmol). The resulting mixture was let stir at 50° C. for 90 min. Solvents were then removed under reduced pressure to afford a brown residue. Half of this material was then dissolved in THF (10 mL) and aqueous ammonium hydroxide (27%) (30 mL, excess) was added. After stirring at 30° C. for 24 h and rt for 18 h, the reaction was diluted with ethyl acetate and the organic layer was washed with water and a saturated brine solution and dried over sodium sulfate. Solvents were removed under reduced pressure and the residue purified by chromatography on SiO2. This material was dissolved in dioxane (6 mL) and 2N NaOH (4 mL) was added in a microwave safe vessel. The reaction was then heated in a microwave at 120° C. for 15 min. The reaction was diluted with EtOAc and the organic layer was washed with water and saturated brine solution and dried over sodium sulfate. Solvents were removed under reduced pressure and the residue purified by chromatography on SiO2 to afford 2-[(2-{[5-[(N,N-dimethylglycyl)(methyl)amino]-4-methyl-2-(methyloxy)phenyl]amino}-1H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]-6-fluorobenzamide (95 mg, 0.182 mmol) as a light green solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 2.10 (s, 6 H) 2.13 (s, 3 H) 2.62 (d, J=15.57 Hz, 1 H) 2.83 (d, J=15.57 Hz, 1 H) 3.04 (s, 3 H) 3.91 (s, 3 H) 6.29 (dd, J=3.20, 1.74 Hz, 1 H) 6.91-7.00 (m, 2H) 7.00-7.07 (m, 1 H) 7.45 (d, J=6.78 Hz, 1 H) 7.54 (s, 1 H) 7.96-8.11 (m, 2 H) 8.23-8.34 (m, 2H) 10.38 (s, 1 H) 11.47 (br. s., 1 H). ESIMS (M+H)+=521.

Provenance & Evidence