Trifluoroacetic acid → HCID 178464314, compound

HRID 2274415Notes

Reaction equation

HRID 2274415 reaction equation
FC(F)(F)C(O)=O.[CH2:8]([N:10]([CH2:42][CH3:43])[C:11]([NH:13][C:14]1[C:15]([C:25]2[NH:29][C:28]3[CH:30]=[C:31]([N:35]4[CH2:40][CH2:39][N:38]([CH3:41])[CH2:37][CH2:36]4)[C:32]([F:34])=[CH:33][C:27]=3[N:26]=2)=[N:16][N:17](C2CCCCO2)[CH:18]=1)=[O:12])[CH3:9]>ClCCl>[CH2:42]([N:10]([CH2:8][CH3:9])[C:11]([NH:13][C:14]1[C:15]([C:25]2[NH:29][C:28]3[CH:30]=[C:31]([N:35]4[CH2:36][CH2:37][N:38]([CH3:41])[CH2:39][CH2:40]4)[C:32]([F:34])=[CH:33][C:27]=3[N:26]=2)=[N:16][NH:17][CH:18]=1)=[O:12])[CH3:43]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 178464303HCID 178464303, compound

Product 1

HCID 178464314HCID 178464314, compoundYield 48.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
22 °C

Procedure

0.7 mL of trifluoroacetic acid is added to a solution of 250 mg of 1,1-diethyl-3-[3-[5-fluoro-6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1-(tetrahydro-pyran-2-yl)-1H-pyrazol-4-yl]urea in solution in 2 mL of dichloromethane. The reaction medium is stirred at 22° C. for 72 hours. The reaction medium is concentrated under vacuum in a rotary evaporator. After evaporation, the reaction crude is purified by flash chromatography on an Intelliflash apparatus on an Analogix RS-12 cartridge. The elution is carried out in pure dichloromethane for 15 min and then in dichloromethane containing 10% of ammoniacal methanol. 100 mg of 1,1-diethyl-3-{3-[5-fluoro-6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-pyrazol-4-yl}urea are obtained in the form of a beige solid. 1H NMR (300 MHz, DMSO-d6, δ in ppm): 1.18 (t, J=7.0 Hz, 6H); 2.90 (s, 3H); 3.05 (m, 2H); 3.28 (m, 2H); 3.38 (q, J=7.0 Hz, 4H); 3.54 (m, 4H); 7.24 (d, J=8.0 Hz, 1H); 7.46 (d, J=11.5 Hz, 1H); 8.00 (s, 1H). EI mass spectrum: m/z=414 (M)+.; m/z=341 (M−C4H11N)+; m/z=114 CF3CO2H+. relative to TFA; m/z=72 C4H10N+; m/z=69 CF3+ relative to TFA; m/z=45 CO2H+ relative to TFA, base peak; m/z=43 C2H5N+.

Workup

  1. concentrationThe reaction medium is concentrated under vacuum in a rotary evaporator
  2. customAfter evaporation
  3. customthe reaction crude
  4. customis purified by flash chromatography on an Intelliflash apparatus on an Analogix RS-12 cartridge
  5. washThe elution
  6. waitis carried out in pure dichloromethane for 15 min

Sources & evidence

ORD record
ord-a3cfccb4d8f6413dbf3c83b3065511a5
Source dataset
uspto-grants-2015_09
Patent number
US09126969B2

Reaction notes

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