3,3,3-Trifluoropropanal → 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

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Reaction Steps

Dissolve N—((S)-6-amino-4,5,6,7-tetrahydro-benzothiazol-2-yl)-3-[4-(4-cyano-phenyl)-pyrazol-1-ylmethyl]-benzamide (0.22 g, 0.48 mmol) and 3,3,3-trifluoropropionaldehyde (0.22 g, 1.94 mmol) and sodium cyanoborohydride (0.12 g, 1.94 mmol) into 5 mL 20% MeOH/CH2Cl2. Add 250 microL of acetic acid and stir overnight at room temperature. Concentrate the mixture and add aq. Na2CO3. Extract 4 times with EtOAc, washed 2 times with aq. Na2CO3 and once with H2O. Dry the organic phase and concentrate to give a clear oil. Purify via SiO2 prep plate chromatography, eluting with 6% MeOH/CH2Cl2/0.5% NH4OH to afford 0.013 g, 4% yield of N-{(S)-6-[bis-(3,3,3-trifluoro-propyl)-amino]-4,5,6,7-tetrahydro-benzothiazol-2-yl}-3-[4-(4-cyano-phenyl)-pyrazol-1-ylmethyl]-benzamide as an oil MS, electrospray 647.8 (M+H), rt 2.11 min. and 147.6 mg, 55% yield 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 as a foamy resin. MS, electrospray 551.69 (M+H), rt 1.58 min.

Provenance & Evidence