Trifluoroacetic acid → HCID 71582697, compound

HRID 1747165Notes

Reaction equation

HRID 1747165 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]([C:26]4[CH2:27][CH2:28][N:29]([C:32]([C@H:34]5[CH2:38][CH2:37][CH2:36][N:35]5C(OC(C)(C)C)=O)=[O:33])[CH2:30][CH:31]=4)[CH:24]=[CH:25][C:20]=3[N:19]=[CH:18]2)[CH3:16])=[C:11]([F:46])[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]([C:26]4[CH2:27][CH2:28][N:29]([C:32]([C@H:34]5[CH2:38][CH2:37][CH2:36][NH:35]5)=[O:33])[CH2:30][CH:31]=4)[CH:24]=[CH:25][C:20]=3[N:19]=[CH:18]2)[CH3:16])=[C:11]([F:46])[CH:10]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86688432HCID 86688432, compound

Product 1

HCID 71582697HCID 71582697, compoundYield 32%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Trifluoroacetic acid (2 mL) was added to a solution of the crude (R)-t-butyl 2-(4-(1-((R)-1-(4-chloro-2-fluorophenyl)ethyl)-1H-benzo[d]imidazol-6-yl)-1,2,3,6-tetrahydropyridine-1-carbonyl)pyrrolidine-1-carboxylate (0.092 g, 0.17 mmol) in dichloromethane (1.5 mL) and stirred at room temperature for 1 h. Excess solvent was removed in vacuo, and the residue was diluted with dichloromethane (15 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, 5-20% methanol in dichloromethane) to give the title compound as a white solid (0.024 g, 0.053 mmol, 32%). 1H NMR (400 MHz, DMSO-d6) δ 9.78-9.70 (m, 1 H), 9.32-9.22 (m, 1 H), 8.44-8.38 (m, 1 H), 7.68 (d, J=8.4 Hz, 1 H), 7.58 (s, 1 H), 7.51-7.41 (m, 3 H), 7.27 (d, J=8.4 Hz, 1 H), 6.17-6.13 (m, 2H), 4.61-4.54 (m, 1 H), 4.19-4.05 (m, 3 H), 3.89-3.85 (m, 1 H), 3.69-3.50 (m, 3 H), 2.52-2.34 (m, 1 H), 1.95 (d, J=6.8 Hz, 3 H), 1.90-1.70 (m, 3 H); MS: (ES) m/z calculated for C25H27ClFN4O [M+H]+453.2, found 453.1.

Workup

  1. customExcess solvent was removed in vacuo
  2. additionthe residue was diluted with dichloromethane (15 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, 5-20% methanol in dichloromethane)

Sources & evidence

ORD record
ord-09a1050820a74f6299e51f679bcd1f61
Source dataset
uspto-grants-2015_10
Patent number
US09150550B2

Reaction notes

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