Reaction #164904

Reaction equation

TFA

4-methyl-3-(9H-pyrimido[4,5-b]indol-7-yl)benzoic acid

N,N,N′,N′-tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate

PF6

5-(trifluoromethyl)pyridin-3-amine

→

4-Methyl-3-(9H-pyrimido[4,5-b]indol-7-yl)-N-[5-(trifluoromethyl)pyridin-3-yl]benzamide

Yield 20.0%

Solvents

CH3CN—H2O

DMF

Conditions

Workup

1. 1
   workup.STIRRINGThe resulting mixture was stirred at 70° C. for 18 h
2. 2
   Otherconsumption of the activated ester (M+H 422)
3. 3
   OtherThe product was isolated by prep HPLC/MS
4. 4
   workup.ADDITIONThe HPLC fractions containing the product
5. 5
   Otherdried
6. 6
   Otherto yield a light yellow solid, 5.6 mg, 20% yield

Procedure

To a vial was added 4-methyl-3-(9H-pyrimido[4,5-b]indol-7-yl)benzoic acid (15.2 mg, 0.0501 mmol), DMF (0.32 mL), and N,N,N′,N′-tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate (22.9 mg, 0.0601 mmol). This mixture was stirred 15 min at RT. To the mixture was then added 5-(trifluoromethyl)pyridin-3-amine (10.6 mg, 0.0651 mmol. The resulting mixture was stirred at 70° C. for 18 h. LCMS indicated complete consumption of the activated ester (M+H 422) and showed product (M+H 448). The product was isolated by prep HPLC/MS using a 19 mm×100 mm C18 column; 28% CH3CN—H2O (0.1% TFA), 1 min, to 48% at 6 min; 30 mL/min. The HPLC fractions containing the product were freeze dried to yield a light yellow solid, 5.6 mg, 20% yield. FMR showed that it was the mono TFA salt; and contained some residual PF6. 1H NMR (DMSO-d6) δ 13.29 (s, 1H, NH); 10.76 (s, 1H, amide NH); 9.72 (s, 1H); 9.22 (s, 1H); 9.20 (s, 1H); 8.69 (s, 1H); 8.62 (s, 1H); 8.44 (d, 1H); 7.98 (m, 2H); 7.66 (s, 1H); 7.56 (d, 1H); 7.53 (d, 1H).

Source