Acetic Acid → HCID 59226969, compound

3-Amino-4-cyano-N[2,6-dimethyl-4-(1,2,2,2-tetrafluoro-1-trifluoromethyl-ethyl)-phenyl]-benzamide (3.01 g, 6.95 mmol) (Example I2) was dissolved in acetonitrile (50 ml) and aqueous formaldehyde (36.5% w/v) (0.64 ml, 6.95 mmol) and acetic acid (30 ml) were added successively. The reaction mixture was stirred at ambient temperature for 45 minutes. Then sodium borohydride (0.44 g, 6.95 mmol) and more acetic acid (5 ml) were added. The reaction mixture was stirred at ambient temperature for 2 hours. The reaction mixture was concentrated. The residue was dissolved in ethyl acetate and the solution washed with aqueous sodium hydroxide (1N). The aqueous phase was extracted three times with ethyl acetate (200 ml). The combined organic extracts were dried over sodium sulfate and concentrated. The residue was purified by column chromatography on silica gel (eluent: cyclohexane/ethyl acetate 1:5) to give 4-cyano-N-[2,6-dimethyl-4-(1,2,2,2-tetrafluoro-1-trifluoromethyl-ethyl)-phenyl]-3-methylamino-benzamide (1.80 g, 58% yield). M.p. 204-206° C. 1H-NMR (400 MHz, CDCl3): 7.53 (d, 1H), 7.37 (s, 3H), 7.23 (s, 1H), 7.10 (q, 1H), 5.88 (d, 1H), 3.02 (d, 3H), 2.35 (s, 6H) ppm. The method as described in Example P1 was then used to prepare Compound No. A3 of Table A.

1. stirringThe reaction mixture was stirred at ambient temperature for 2 hours
2. concentrationThe reaction mixture was concentrated
3. dissolutionThe residue was dissolved in ethyl acetate
4. washthe solution washed with aqueous sodium hydroxide (1N)
5. extractionThe aqueous phase was extracted three times with ethyl acetate (200 ml)
6. dry with materialThe combined organic extracts were dried over sodium sulfate
7. concentrationconcentrated
8. customThe residue was purified by column chromatography on silica gel (eluent: cyclohexane/ethyl acetate 1:5)

ORD record

ord-e18b5226406c4885801829f931100f9e

Source dataset

uspto-grants-2012_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08247594B2