Trifluoroacetic acid → HCID 86688449, compound

HRID 2359138Notes

Reaction equation

HRID 2359138 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])[C@H:29]([CH3:47])[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[CH2:32][CH2:31][N:30]([C:33]([C@H:35]4[CH2:39][CH2:38][CH2:37][NH:36]4)=[O:34])[C@H:29]([CH3:47])[CH2:28]3)[CH:25]=2)[CH:20]=[N:19]1)[CH3:17]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86688451HCID 86688451, compound

Product 1

HCID 86688449HCID 86688449, compoundYield 94%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Trifluoroacetic acid (0.5 mL) was added to a solution of (R)-t-butyl 2-((R)-4-(1-((R)-1-(2,4-dichlorophenyl)ethyl)-1H-indazol-6-yl)-2-methylpiperazine-1-carbonyl)pyrrolidine-1-carboxylate (0.030 g, 0.050 mmol) in dichloromethane (2 mL) 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, 0-10% methanol in dichloromethane) to give the title compound as a white solid (0.023 g, 0.047 mmol, 93%). 1H NMR (400 MHz, CDCl3) δ 7.84 (s, 1 H), 7.56 (dd, J=4.0, 8.4 Hz, 1 H), 7.38 (d, J=2.4 Hz, 1 H), 7.17-7.10 (m, 2 H), 6.84-6.81 (m, 1 H), 6.61 (d, J=9.6 Hz, 1 H), 6.08 (q, J=7.2 Hz, 1 H), 4.87-4.68 (m, 2 H), 4.52-4.14 (m, 1 H), 3.67-3.53 (m, 3 H), 3.50-3.21 (m, 3 H), 3.04-2.91 (m, 1 H), 2.82-2.76 (m, 1 H), 2.62-2.55 (m, 1 H), 2.28-2.20 (m, 1 H), 2.13-2.02 (m, 1 H), 1.99 (d, J=6.8 Hz, 3 H), 1.53 and 1.40 (d, J=6.4 and 6.8 Hz, 3 H); MS: (ES) m/z calculated for C25H30Cl2N5O [M+H]+ 486.2, found 486.4.

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, 0-10% methanol in dichloromethane)

Sources & evidence

ORD record
ord-128ce464cc344a4ab8461ae049e8fe81
Source dataset
uspto-grants-2014_04
Patent number
US08685959B2

Reaction notes

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