Trifluoroacetic acid → HCID 86688433, compound

HRID 1747167Notes

Reaction equation

HRID 1747167 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][CH2:28]3)[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[CH2:28][CH2:29][N:30]([C:33]([C@H:35]4[CH2:39][CH2:38][CH2:37][NH:36]4)=[O:34])[CH2:31][CH2:32]3)[CH:25]=[CH:26][C:21]=2[N:20]=[CH:19]1)[CH3:17]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86688435HCID 86688435, compound

Product 1

HCID 86688433HCID 86688433, compoundYield 38.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Trifluoroacetic acid (0.5 mL) was added to a solution of (R)-t-butyl 2-(4-(1-((R)-1-(2,4-dichlorophenyl)ethyl)-1H-benzo[d]imidazol-6-yl)piperazine-1-carbonyl)pyrrolidine-1-carboxylate (0.036 g, 0.062 mmol) in dichloromethane (1 mL), and the reaction mixture 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, 15% methanol in dichloromethane) to give the desired compound (0.011 g, 0.024 mmol, 38%). The material was dissolved in acetonitrile and treated with 1 N aqueous hydrochloric acid solution (0.048 mL, 0.048 mmol). The solution was lyophilized to give the di-HCl salt as the title compound as a white solid. 1H NMR (400 MHz, DMSO-d6) δ 10.02-9.92 (m, 1 H), 9.53 (s, 1 H), 8.49-8.42 (m, 1 H), 7.74 (d, J=2.0, 1 H), 7.69 (d, J=8.8 Hz, 1 H), 7.57 (d, J=8.8 Hz, 1 H), 7.51 (dd, J=1.6, 8.4 Hz, 1 H), 7.35 (d, J=9.2 Hz, 1 H), 6.98 (s, 1 H), 6.24 (q, J=6.8 Hz, 1H), 4.65-4.62 (m, 1H), 3.67-3.63 (m, 5 H), 3.22-3.16 (m, 4 H), 2.39-2.34 (m, 2 H), 1.97 (d, J=6.8 Hz, 3 H), 1.93-1.78 (m, 3 H); MS: (ES) m/z calculated for C24H28Cl2N5O [M+H]+ 472.2, found 472.1.

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, 15% methanol in dichloromethane)

Sources & evidence

ORD record
ord-d40e0eff6b904350ac3851b04b726af7
Source dataset
uspto-grants-2015_10
Patent number
US09150550B2

Reaction notes

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