反应详情

Stir a solution of 3-[4-(4-cyano-phenyl)-pyrazol-1-ylmethyl]-N—[(S)-6-(3,3,3-trifluoro-propylamino)-4,5,6,7-tetrahydro-benzothiazol-2-yl]-benzamide (0.063 g, 0.11 mmol) and formaldehyde solution (0.08 mL, 1.14 mmol, 37 wt % in H2O) and sodium cyanoborohydride (0.014 g, 0.23 mmol) in 1 mL 20% MeOH/CH2Cl2 overnight at room temperature in a capped flask. Concentrate the mixture, add aq. H2O and extract the product 4×EtOAc, washed 3×H2O. Dry the mixture with a drying agent and concentrate. Purify the product on a prep plate eluting with 5% MeOH/CH2Cl2 which affords 0.052 g, 80% yield of 3-[4-(4-cyano-phenyl)-pyrazol-1-ylmethyl]-N-{(S)-6-[methyl-(3,3,3-trifluoro-propyl)-amino]-4,5,6,7-tetrahydro-benzothiazol-2-yl}-benzamide as a clear resin. MS, electrospray 565.71 (M+H), room temperature 1.60 min. The following compound is prepared analogously (Example 11)

1. concentrationConcentrate the mixture
2. additionadd aq. H2O
3. extractionextract the product 4×EtOAc
4. washwashed 3×H2O
5. customDry the mixture with a drying agent
6. concentrationconcentrate
7. customPurify the product on a prep plate
8. washeluting with 5% MeOH/CH2Cl2 which