Trifluoroacetic acid → HCID 86688448, compound

HRID 2359136Notes

Reaction equation

HRID 2359136 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]([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]=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]([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]=2)[CH:20]=[N:19]1)[CH3:17]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86688446HCID 86688446, compound

Product 1

HCID 86688448HCID 86688448, compoundYield 59.1%

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)piperazine-1-carbonyl)pyrrolidine-1-carboxylate (0.052 g, 0.088 mmol) in dichloromethane (2 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, 30% methanol in dichloromethane) to give the title compound as a white solid (0.025 g, 0.052 mmol, 57%). 1H NMR (400 MHz, CDCl3) δ 7.94 (s, 1 H), 7.58 (d, J=9.2 Hz, 1 H), 7.38 (d, J=2.0 Hz, 1 H), 7.16-7.09 (m, 2 H), 6.86 (dd, J=2.0, 8.0 Hz, 1 H), 6.64 (s, 1 H), 6.10 (q, J=6.8 Hz, 1 H), 4.35 (dd, J=6.4, 8.4 Hz, 1 H), 3.91-3.85 (m, 1 H), 3.80-3.60 (m, 3 H), 3.31-3.11 (m, 6 H), 2.36-2.28 (m, 1 H), 1.99 (d, J=6.8 Hz, 3 H), 1.87-1.80 (m, 3 H); MS: (ES) m/z calculated for C24H28Cl2N5O [M+H]+ 472.2, found 472.4.

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, 30% methanol in dichloromethane)

Sources & evidence

ORD record
ord-0643525d664e475b9ad3282a5f07d84b
Source dataset
uspto-grants-2014_04
Patent number
US08685959B2

Reaction notes

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