Trifluoroacetic acid → HCID 86688443, compound

HRID 1747176Notes

Reaction equation

HRID 1747176 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:26]2[C:21](=[CH:22][CH:23]=[C:24]([C:27]3[CH2:28][CH2:29][N:30]([C:33]([C@H:35]4[CH2:39][CH2:38][CH2:37][N:36]4C(OC(C)(C)C)=O)=[O:34])[CH2:31][CH:32]=3)[CH:25]=2)[CH:20]=[N: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:26]2[C:21](=[CH:22][CH:23]=[C:24]([C: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][CH:32]=3)[CH:25]=2)[CH:20]=[N:19]1)[CH3:17]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86688445HCID 86688445, compound

Product 1

HCID 86688443HCID 86688443, compoundYield 38.5%

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-indazol-6-yl)-1,2,3,6-tetrahydropyridine-1-carbonyl)pyrrolidine-1-carboxylate (0.037 g, 0.065 mmol) in dichloromethane (1 mL) and the resulting solution was stirred at room temperature for 30 min. 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 title compound as a white solid (0.012 g, 0.025 mmol, 38%). 1H NMR (400 MHz, CDCl3) δ 8.01 (s, 1 H), 7.66 (d, J=8.0 Hz, 1 H), 7.39 (s, 1 H), 7.19-7.12 (m, 4 H), 6.20 (d, J=6.8 Hz, 1 H), 6.11-6.08 (m, 1 H), 4.82-4.74 (m, 1 H), 4.29-4.09 (m, 2 H), 3.98-3.70 (m, 2 H), 3.46-3.34 (m, 3 H), 2.70-2.48 (m, 3 H), 2.16-1.98 (m, 3 H), 2.00 (d, J=7.2 Hz, 3H); MS: (ES) m/z calculated for C25H27Cl2N4O [M+H]+ 469.2, found 469.4.

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-45147cd12f7e431c8cd4678c20688c43
Source dataset
uspto-grants-2015_10
Patent number
US09150550B2

Reaction notes

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