HCID 136374763, compound → HCID 178522443, compound

HRID 2274407Notes

Reaction equation

HRID 2274407 reaction equation
[F:1][C:2]1[C:3]([O:31][CH2:32][CH2:33][CH2:34][CH2:35][N:36]2[CH2:41][CH2:40][CH2:39][CH2:38][CH2:37]2)=[CH:4][C:5]2[N:9]=[C:8]([C:10]3[C:14]([NH:15][C:16]([N:18]4[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]4)=[O:17])=[CH:13][N:12](C4CCCCO4)[N:11]=3)[NH:7][C:6]=2[CH:30]=1>ClCCl.FC(F)(F)C(O)=O>[F:1][C:2]1[C:3]([O:31][CH2:32][CH2:33][CH2:34][CH2:35][N:36]2[CH2:41][CH2:40][CH2:39][CH2:38][CH2:37]2)=[CH:4][C:5]2[N:9]=[C:8]([C:10]3[C:14]([NH:15][C:16]([N:18]4[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]4)=[O:17])=[CH:13][NH:12][N:11]=3)[NH:7][C:6]=2[CH:30]=1

Participants

4

Reactant 1

HCID 136374763HCID 136374763, compound

Product 1

HCID 178522443HCID 178522443, compoundYield 77.7%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 6422Trifluoroacetic acidSolvent

Procedure

A solution of 130 mg of piperidine-1-carboxylic acid [3-[6-fluoro-5-(4-piperidin-1-ylbutoxy)-1H-benzimidazol-2-yl]-1-(tetrahydropyran-2-yl)-1H-pyrazol-4-yl]amide in 2 mL of dichloromethane and 500 μL of trifluoroacetic acid are stirred for 72 hours at ambient temperature. After evaporation of the solvent under vacuum in a rotary evaporator, the reaction crude is purified by flash chromatography on an Analogix RS-12 cartridge with an eluent of 100% dichloromethane to 90/10 dichloromethane/methanol. 86 mg of N-{3-[6-fluoro-5-(4-piperidin-1-ylbutoxy)-1H-benzimidazol-2-yl]-1H-pyrazol-4-yl}piperidine-1-carboxamide in the form of a trifluoroacetate salt are obtained in the form of a yellow solid. 1H NMR (300 MHz, DMSO-d6, δ in ppm): for this batch, we observe a 60%-40% resolution of tautomers with: from 1.20 to 1.94 (broad m, 16H); from 2.70 to 3.43 (m partially masked, 6H); 3.50 (m, 4H); 4.11 (m, 2H); 7.11 (d, J=7.5 Hz, 0.6H); 7.27 (d, J=11.0 Hz, 0.4H); 7.37 (d, J=7.5 Hz, 0.4H); 7.51 (d, J=11.0 Hz, 0.6H); 8.01 (broad s, 1H); 8.94 (broad m, 1H); 9.83 (s, 0.4H); 9.87 (s, 0.6H); 12.95 (s, 0.4H); 13.0 (s, 0.6H); 13.05 (s, 1H).

Workup

  1. customAfter evaporation of the solvent under vacuum
  2. customin a rotary evaporator
  3. customthe reaction crude
  4. customis purified by flash chromatography on an Analogix RS-12 cartridge with an eluent of 100% dichloromethane to 90/10 dichloromethane/methanol

Sources & evidence

ORD record
ord-daca0dd7fab3458bba4aa46d6486adb2
Source dataset
uspto-grants-2015_09
Patent number
US09126969B2

Reaction notes

Loading…