Trifluoroacetic acid → HCID 178480619, compound

HRID 2274414Notes

Reaction equation

HRID 2274414 reaction equation
FC(F)(F)C(O)=O.[F:8][C:9]1[C:37]([N:38]2[CH2:43][CH2:42][N:41]([CH3:44])[CH2:40][CH2:39]2)=[CH:36][C:12]2[NH:13][C:14]([C:16]3[C:20]([NH:21][C:22]([N:24]4[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]4)=[O:23])=[CH:19][N:18](C4CCCCO4)[N:17]=3)=[N:15][C:11]=2[CH:10]=1>ClCCl>[F:8][C:9]1[C:37]([N:38]2[CH2:39][CH2:40][N:41]([CH3:44])[CH2:42][CH2:43]2)=[CH:36][C:12]2[NH:13][C:14]([C:16]3[C:20]([NH:21][C:22]([N:24]4[CH2:25][CH2:26][CH2:27][CH2:28][CH2:29]4)=[O:23])=[CH:19][NH:18][N:17]=3)=[N:15][C:11]=2[CH:10]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 178480618HCID 178480618, compound

Product 1

HCID 178480619HCID 178480619, compoundYield 55.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
22 °C

Procedure

0.6 mL of trifluoroacetic acid is added to a solution of 260 mg of piperidine-1-carboxylic acid [3-[5-fluoro-6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1-(tetrahydropyran-2-yl)-1H-pyrazol-4-yl]amide in solution in 1.5 mL of dichloromethane. The reaction medium is stirred at 22° C. for 48 hours. The reaction medium is concentrated under vacuum in a rotary evaporator. After evaporation, the reaction crude is purified by flash chromatography in an Intelliflash apparatus on an Analogix RS-12 cartridge. The elution is carried out in pure dichloromethane for 20 min and then in dichloromethane containing 10% of ammoniacal methanol. 120 mg of N-{3-[5-fluoro-6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-pyrazol-4-yl}piperidine-1-carboxamide are obtained in the form of a beige solid. 1H NMR (400 MHz, DMSO-d6, δ in ppm): from 1.45 to 1.70 (m, 6H); 2.90 (s, 3H); 3.07 (m, 2H); 3.29 (m, 2H); 3.45 (m, 4H); 3.55 (m, 4H); 7.31 (d, J=8.0 Hz, 1H); 7.57 (d, J=11.5 Hz, 1H); 8.02 (s, 1H). EI mass spectrum: m/z=426, M+., m/z=341 (M−C5H11N)+; m/z=114 CF3CO2H+. relative to TFA; m/z=84 C5H10N+; m/z=69 CF3+ relative to TFA; m/z=45 CO2H+ relative to TFA base peak, m/z=43 C2H5N+.; m/z=41 C3H5+

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 in an Intelliflash apparatus on an Analogix RS-12 cartridge
  5. washThe elution
  6. waitis carried out in pure dichloromethane for 20 min

Sources & evidence

ORD record
ord-b9cd1b021a1640c2b5497d7c94fbb4f1
Source dataset
uspto-grants-2015_09
Patent number
US09126969B2

Reaction notes

Loading…