Trifluoroacetic acid → HCID 178464320, compound

HRID 2274406Notes

Reaction equation

HRID 2274406 reaction equation
[CH2:1]([N:3]([CH2:39][CH3:40])[C:4]([NH:6][C:7]1[C:8]([C:18]2[NH:22][C:21]3[CH:23]=[C:24]([F:38])[C:25]([O:27][CH2:28][CH2:29][CH2:30][CH2:31][N:32]4[CH2:37][CH2:36][CH2:35][CH2:34][CH2:33]4)=[CH:26][C:20]=3[N:19]=2)=[N:9][N:10](C2CCCCO2)[CH:11]=1)=[O:5])[CH3:2].FC(F)(F)C(O)=O>ClCCl>[CH2:39]([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]([F:38])[C:25]([O:27][CH2:28][CH2:29][CH2:30][CH2:31][N:32]4[CH2:33][CH2:34][CH2:35][CH2:36][CH2:37]4)=[CH:26][C:20]=3[N:19]=2)=[N:9][NH:10][CH:11]=1)=[O:5])[CH3:40]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 136374995HCID 136374995, compound

Product 1

HCID 178464320HCID 178464320, compoundYield 84.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

100 mg of 1,1-diethyl-3-[3-[6-fluoro-5-(4-piperidin-1-ylbutoxy)-1H-benzimidazol-2-yl]-1-(tetrahydropyran-2-yl)-1H-pyrazol-4-yl}urea in solution in 2 mL of dichloromethane with 1 mL of trifluoroacetic acid are stirred at ambient temperature for 18 hours. The solvent is evaporated off under vacuum by flash chromatography on an Intelliflash apparatus on an Analogix RS-12 cartridge with an eluent of 100% dichloromethane to 85/15 dichloromethane/methanol. 72 mg of 1,1-diethyl-3-{3-[6-fluoro-5-(4-piperidin-1-ylbutoxy)-1H-benzimidazol-2-yl]-1H-pyrazol-4-yl}urea in the form of a trifluoroacetate salt 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: 1.23 (m, 6H); from 1.30 to 1.91 (broad m, 10H); 2.70 to 3.53 (very broad m, 6H); 3.41 (m, 4H); 4.12 (m, 2H); 7.11 (d, J=8.0 Hz, 0.6H); from 7.24 to 7.30 (m, 0.8H); 7.44 (d, J=11.0 Hz, 0.6H); 8.00 (s, 1H); 8.94 (broad m, 1H); 9.77 (s, 0.4H); 9.79 (s, 0.6H); 12.9 (broad s, 0.4H); 12.95 (broad s, 0.6H); 13.0 (broad s, 1H).

Workup

  1. customThe solvent is evaporated off under vacuum by flash chromatography on an Intelliflash apparatus on an Analogix RS-12 cartridge with an eluent of 100% dichloromethane to 85/15 dichloromethane/methanol

Sources & evidence

ORD record
ord-0f10c2c86daf4a799f25ddf7dcccf974
Source dataset
uspto-grants-2015_09
Patent number
US09126969B2

Reaction notes

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