Trifluoroacetic acid → HCID 71582012, compound

HRID 2359127Notes

Reaction equation

HRID 2359127 reaction equation
FC(F)(F)C(O)=O.[Cl:8][C:9]1[CH:14]=[CH:13][C:12]([C@H:15]([N:17]2[C:21]3[CH:22]=[C:23]([N:26]4[CH2:31][CH2:30][N:29]([C:32]([C@H:34]5[CH2:38][CH2:37][CH2:36][N:35]5C(OC(C)(C)C)=O)=[O:33])[C@H:28]([CH3:46])[CH2:27]4)[CH:24]=[CH:25][C:20]=3[N:19]=[CH:18]2)[CH3:16])=[C:11]([F:47])[CH:10]=1>ClCCl>[Cl:8][C:9]1[CH:14]=[CH:13][C:12]([C@H:15]([N:17]2[C:21]3[CH:22]=[C:23]([N:26]4[CH2:31][CH2:30][N:29]([C:32]([C@H:34]5[CH2:38][CH2:37][CH2:36][NH:35]5)=[O:33])[C@H:28]([CH3:46])[CH2:27]4)[CH:24]=[CH:25][C:20]=3[N:19]=[CH:18]2)[CH3:16])=[C:11]([F:47])[CH:10]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86688438HCID 86688438, compound

Product 1

HCID 71582012HCID 71582012, compoundYield 44%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Trifluoroacetic acid (0.5 mL) was added to a solution of (R)-t-butyl 2-((R)-4-(1-((R)-1-(4-chloro-2-fluorophenyl)ethyl)-1H-benzo[d]imidazol-6-yl)-2-methylpiperazine-1-carbonyl)pyrrolidine-1-carboxylate (0.022 g, 0.039 mmol) in dichloromethane (2 mL) and the resulting solution was stirred at room temperature for 1 h. Excess solvent was removed in vacuo, and the residue was diluted with dichloromethane (10 mL). The organic layer was neutralized with saturated aqueous sodium bicarbonate, and the aqueous layer was further extracted with dichloromethane (2×15 mL). The combined organic layers were dried (Na2SO4), filtered, and concentrated in vacuo. The crude product was purified by flash chromatography (SiO2, 0-25% methanol in dichloromethane) to give the title compound as a white solid (0.008 g, 0.017 mmol, 44%). 1H NMR (400 MHz, CDCl3) δ 8.03 (s, 1 H), 7.67 (dd, J=4.0, 8.8 Hz, 1 H), 7.13 (d, J=10.0 Hz, 1 H), 7.06 (d, J=8.4 Hz, 1 H), 6.94-6.87 (m, 2 H), 6.58 (d, J=6.8 Hz, 1 H), 5.77 (q, J=6.8 Hz, 1 H), 4.71-4.78 (m, 1 H), 4.51-4.12 (m, 1 H), 3.64-3.62 (m, 1 H), 3.50-3.31 (m, 5 H), 3.26-3.20 (m, 1 H), 2.96-2.84 (m, 1 H), 2.74-2.70 (m, 1 H), 2.54-2.46 (m, 1 H), 2.15-2.02 (m, 2 H), 1.99 (d, J=6.8 Hz, 3 H), 1.52 and 1.38 (d, J=6.4 and 6.8 Hz, 3 H); MS: (ES) m/z calculated for C25H30ClFN5O [M+H]+ 470.2, found 470.3.

Workup

  1. customExcess solvent was removed in vacuo
  2. additionthe residue was diluted with dichloromethane (10 mL)
  3. extractionthe aqueous layer was further extracted with dichloromethane (2×15 mL)
  4. dry with materialThe combined organic layers were dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude product was purified by flash chromatography (SiO2, 0-25% methanol in dichloromethane)

Sources & evidence

ORD record
ord-f6ffbcf2a4a64be7a9d97271674ff3de
Source dataset
uspto-grants-2014_04
Patent number
US08685959B2

Reaction notes

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