Formaldehyde → Trifluoroacetic acid

HRID 912534Notes

Reaction equation

HRID 912534 reaction equation
[F:1][C:2]1([CH2:8][CH2:9][O:10][C:11]2[CH:16]=[CH:15][C:14]([C:17]3[N:22]=[C:21]([C:23]#[N:24])[C:20]4[N:25]=[CH:26][N:27]([CH3:28])[C:19]=4[CH:18]=3)=[CH:13][C:12]=2[C:29]([F:32])([F:31])[F:30])[CH2:7][CH2:6][NH:5][CH2:4][CH2:3]1.C=O.[C:35]([BH3-])#N.[Na+].[C:39](=[O:42])(O)[O-:40].[Na+]>C(#N)C.C1COCC1.C(O)(=O)C>[F:1][C:2]1([CH2:8][CH2:9][O:10][C:11]2[CH:16]=[CH:15][C:14]([C:17]3[N:22]=[C:21]([C:23]#[N:24])[C:20]4[N:25]=[CH:26][N:27]([CH3:28])[C:19]=4[CH:18]=3)=[CH:13][C:12]=2[C:29]([F:30])([F:31])[F:32])[CH2:7][CH2:6][N:5]([CH3:35])[CH2:4][CH2:3]1.[C:39]([OH:40])([C:29]([F:32])([F:31])[F:30])=[O:42]

Participants

8

Reactant 4

HCID 712FormaldehydeHCID 516892Sodium BicarbonateHCID 5003444Sodium cyanoborohydrideHCID 59410632HCID 59410632, compound

Product 2

HCID 6422Trifluoroacetic acidHCID 46842744HCID 46842744, compound

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 22177404Acetonitrile tetrahydrofuranSolvent

Procedure

To 6-(4-(2-(4-fluoropiperidin-4-yl)ethoxy)-3-(trifluoromethyl)phenyl)-1-methyl-1H-imidazo[4,5-c]pyridine-4-carbonitrile (TFA salt, 100 mg) in acetonitrile/THF (2 ml, 1:1) was added formaldehyde (37%, 140 ul), acetic acid (0.3 ml), followed by sodium cyanoborohydride (100 mg). The mixture was stirred at room temperature for 2 hours, and then poured to aqueous sodium bicarbonate (10 ml). The mixture was then extracted with ethyl acetate (20 ml+10 ml×4). Combined organic layer was then dried over sodium sulphate. After removal of solvent under reduced pressure, the residue was purified by HPLC to give 6-(4-(2-(4-fluoro-1-methyl-piperidin-4-yl)ethoxy)-3-(trifluoromethyl)phenyl)-1-methyl-1H-imidazo[4,5-c]pyridine-4-carbonitrile as a TFA salt. 1H NMR (CD3OD) δ: 8.45 (s, 1H), 8.38 (s, 2H), 8.35 (d, 1H), 7.35 (d, 1H), 4.39 (t, 2H), 4.02 (s, 3H), 3.50 (m, 2H), 3.3 (m, 2H), 2.93 (s, 3H), 2.25-2.4 (m, 4H), 2.0-2.25 (m, 2H). MS m/z 462 (M+H).

Workup

  1. extractionThe mixture was then extracted with ethyl acetate (20 ml+10 ml×4)
  2. dry with materialCombined organic layer was then dried over sodium sulphate
  3. customAfter removal of solvent under reduced pressure
  4. customthe residue was purified by HPLC

Sources & evidence

ORD record
ord-73e5810ee9a841d28db022356db32fee
Source dataset
uspto-grants-2011_09
Patent number
US08026236B2

Reaction notes

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