Trifluoroacetic acid → HCID 178464319, compound

HRID 2274389Notes

Reaction equation

HRID 2274389 reaction equation
[CH2:1]([N:3]([CH2:37][CH3:38])[C:4]([NH:6][C:7]1[C:8]([C:18]2[NH:22][C:21]3[CH:23]=[C:24]([O:28][CH2:29][CH2:30][N:31]4[CH2:36][CH2:35][CH2:34][CH2:33][CH2:32]4)[C:25]([F:27])=[CH:26][C:20]=3[N:19]=2)=[N:9][N:10](C2CCCCO2)[CH:11]=1)=[O:5])[CH3:2].[F:39][C:40]([F:45])([F:44])[C:41]([OH:43])=[O:42]>ClCCl>[F:39][C:40]([F:45])([F:44])[C:41]([OH:43])=[O:42].[CH2:37]([N:3]([CH2:1][CH3:2])[C:4]([NH:6][C:7]1[C:8]([C:18]2[NH:22][C:21]3[CH:23]=[C:24]([O:28][CH2:29][CH2:30][N:31]4[CH2:36][CH2:35][CH2:34][CH2:33][CH2:32]4)[C:25]([F:27])=[CH:26][C:20]=3[N:19]=2)=[N:9][NH:10][CH:11]=1)=[O:5])[CH3:38]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acid2×HCID 178464309HCID 178464309, compound

Product 1

HCID 178464319HCID 178464319, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 38 mg of 1,1-diethyl-3-{3-[5-fluoro-6-(2-piperidin-1-ylethoxy)-1H-benzimidazol-2-yl]-1-(tetrahydropyran-2-yl)-1H-pyrazol-4-yl}urea is solubilized in 2 mL of dichloromethane and then 500 μl of trifluoroacetic acid are added. The reaction medium is stirred at ambient temperature overnight. The solvent is evaporated off under vacuum in a rotary evaporator and the crude is reacted again in 500 μL of dichloromethane and 500 μL of trifluoroacetic acid at ambient temperature for one hour. After concentration of the solvent in a rotary evaporator, the reaction crude is purified by flash chromatography on a 4 g silica cartridge, eluent: 100/0 to 90/10 dichloromethane/-methanol. 20 mg of 1,1-diethyl-3-{3-[5-fluoro-6-(2-piperidin-1-ylethoxy)-1H-benzimidazol-2-yl]-1H-pyrazol-4-yl}urea trifluoroacetate are isolated in the form of a yellow solid. 1H NMR (400 MHz, DMSO-d6, δ in ppm), for this batch, we observe a 60%-40% resolution of tautomers with: 1.24 (m, 6H); from 1.32 to 1.93 (m, 6H); 3.06 (broad m, 2H); from 3.23 to 3.68 (broad m, 4H); 3.41 (m, 4H); 4.44 (broad m, 2H); 7.21 (d, J=8.0 Hz, 0.6H); 7.32 (d, J=11.0 Hz, 0.4H); 7.38 (d, J=8.0 Hz, 0.4H); 7.49 (d, J=11.0 Hz, 0.6H); 8.01 (s, 1H); 9.32 (broad m, 1H); 9.74 (s, 0.4H); 9.77 (s, 0.6H); 13.0 (s, 1.6H); 13.05 (s, 0.4H).

Workup

  1. customThe solvent is evaporated off under vacuum in a rotary evaporator
  2. customthe crude is reacted again in 500 μL of dichloromethane
  3. customAfter concentration of the solvent in a rotary evaporator
  4. customthe reaction crude
  5. customis purified by flash chromatography on a 4 g silica cartridge, eluent

Sources & evidence

ORD record
ord-70c7d2da69724488ba3a52d874f6f711
Source dataset
uspto-grants-2015_09
Patent number
US09126969B2

Reaction notes

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