Trifluoroacetic acid → HCID 71581734, compound

HRID 1747171Notes

Reaction equation

HRID 1747171 reaction equation
FC(F)(F)C(O)=O.[Cl:8][C:9]1[CH:14]=[C:13]([Cl:15])[CH:12]=[CH:11][C:10]=1[C@H:16]([N:18]1[C:22]2[CH:23]=[C:24]([N:27]3[CH2:32][CH2:31][N:30]([C:33]([C@H:35]4[CH2:39][CH2:38][CH2:37][N:36]4C(OC(C)(C)C)=O)=[O:34])[CH2:29][C@H:28]3[CH3:47])[CH:25]=[CH:26][C:21]=2[N:20]=[CH:19]1)[CH3:17]>ClCCl>[Cl:8][C:9]1[CH:14]=[C:13]([Cl:15])[CH:12]=[CH:11][C:10]=1[C@H:16]([N:18]1[C:22]2[CH:23]=[C:24]([N:27]3[CH2:32][CH2:31][N:30]([C:33]([C@H:35]4[CH2:39][CH2:38][CH2:37][NH:36]4)=[O:34])[CH2:29][C@H:28]3[CH3:47])[CH:25]=[CH:26][C:21]=2[N:20]=[CH:19]1)[CH3:17]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86688439HCID 86688439, compound

Product 1

HCID 71581734HCID 71581734, compoundYield 21%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Trifluoroacetic acid (0.5 mL) was added to a solution of the crude (R)-t-butyl 2-((R)-4-(1-((R)-1-(2,4-dichlorophenyl)ethyl)-1H-benzo[d]imidazol-6-yl)-3-methylpiperazine-1-carbonyl)pyrrolidine-1-carboxylate in dichloromethane (2.0 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 (5 mL). The organic layer was neutralized with saturated aqueous sodium bicarbonate, and the aqueous layer was further extracted with dichloromethane (2×10 mL). The combined organic layers were dried (Na2SO4), filtered, and concentrated in vacuo. The crude product was purified by flash chromatography (SiO2, 20% 7 N ammonia/methanol in dichloromethane) to give the title compound as a white solid (0.011 g, 0.023 mmol, 21% for 2 steps). 1H NMR (400 MHz, CDCl3) δ 8.07 (d, J=2.8 Hz, 1 H), 7.69 (dd, J=4.0, 8.8 Hz, 1 H), 7.45 (dd, J=2.0, 2.0 Hz, 1 H), 7.14 (dd, J=2.0, 8.4 Hz, 1 H), 6.99-6.95 (m, 1 H), 6.83 (dd, J=4.8, 8.4 Hz, 1 H), 6.59 (dd, J=2.0, 18.4 Hz, 1 H), 5.90 (q, J=6.8 Hz, 1 H), 4.45-4.35 (m, 1 H), 3.82-3.43 (m, 4 H), 3.32-3.17 (m, 2 H), 3.11-2.94 (m, 2 H), 2.39-2.28 (m, 2 H), 1.98 (dd, J=2.4, 6.8 Hz, 3 H), 1.94-1.80 (m, 3 H), 0.90 and 0.81 (d, J=6.4 and 6.0 Hz, 3 H); MS: (ES) m/z calculated for C25H30Cl2N5O [M+H]+ 486.2, found 485.

Workup

  1. customExcess solvent was removed in vacuo
  2. additionthe residue was diluted with dichloromethane (5 mL)
  3. extractionthe aqueous layer was further extracted with dichloromethane (2×10 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, 20% 7 N ammonia/methanol in dichloromethane)

Sources & evidence

ORD record
ord-5205cee31b1b400286c027efd3bb8015
Source dataset
uspto-grants-2015_10
Patent number
US09150550B2

Reaction notes

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