Trifluoroacetic acid → Cyclohexyl-[6-fluoro-5-(5-methyl-1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-pyridin-2-yl]-amine

HRID 1396162Notes

Reaction equation

[F:1][C:2]1[N:7]=[C:6]([NH2:8])[CH:5]=[CH:4][C:3]=1[CH2:9][C:10]1[C:18]2[C:13](=[N:14][CH:15]=[C:16]([CH3:19])[CH:17]=2)[NH:12][CH:11]=1.[C:20]1(=O)[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]1.C([SiH](CC)CC)C.FC(F)(F)C(O)=O>C(#N)C>[CH:20]1([NH:8][C:6]2[CH:5]=[CH:4][C:3]([CH2:9][C:10]3[C:18]4[C:13](=[N:14][CH:15]=[C:16]([CH3:19])[CH:17]=4)[NH:12][CH:11]=3)=[C:2]([F:1])[N:7]=2)[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]1

Participants

Conditions

Temperature: 80 °C

Procedure

To 6-fluoro-5-(5-methyl-1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-pyridin-2-ylamine (49, 100 mg, 0.39 mmol) and cyclohexanone (67, 0.0465 mL, 0.449 mmol) in 3.00 mL of acetonitrile, triethylsilane (0.400 mL, 2.50 mmol) and trifluoroacetic acid (0.300 mL, 3.89 mmol) were added. The reaction was stirred at 80° C. overnight, then extracting with ethyl acetate and 1N aqueous sodium bicarbonate. The organic layer was washed with brine, dried with magnesium sulfate, filtered and the filtrate concentrated under vacuum. The resulting material was purified by silica gel column chromatography, eluting with 0-60% ethyl acetate in hexane. Appropriate fractions were combined and concentrated under vacuum to provide the desired compound (P-3008, 115 mg). MS (ESI) [M+H+]+=339.0.

Workup

extractionextracting with ethyl acetate and 1N aqueous sodium bicarbonate
washThe organic layer was washed with brine
dry with materialdried with magnesium sulfate
filtrationfiltered
concentrationthe filtrate concentrated under vacuum
customThe resulting material was purified by silica gel column chromatography
washeluting with 0-60% ethyl acetate in hexane
concentrationconcentrated under vacuum

Sources & evidence

ORD record: ord-02898b14c50344e58a522505102349a1
Source dataset: uspto-grants-2014_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08901118B2

Reaction notes

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