Trifluoroacetic acid → FT-1101 free base

HRID 1051602Notes

Reaction equation

HRID 1051602 reaction equation
FC(F)(F)C(O)=O.[CH:8]1([O:12][C:13]2[C:22]([C:23]3[CH:24]=[N:25][N:26]([CH:28]4[CH2:33][CH2:32][N:31](C(OC(C)(C)C)=O)[CH2:30][CH2:29]4)[CH:27]=3)=[CH:21][CH:20]=[C:19]3[C:14]=2[CH2:15][CH2:16][C@H:17]([CH3:46])[N:18]3[C:41]([CH:43]2[CH2:45][CH2:44]2)=[O:42])[CH2:11][CH2:10][CH2:9]1>ClCCl>[CH:8]1([O:12][C:13]2[C:22]([C:23]3[CH:24]=[N:25][N:26]([CH:28]4[CH2:29][CH2:30][NH:31][CH2:32][CH2:33]4)[CH:27]=3)=[CH:21][CH:20]=[C:19]3[C:14]=2[CH2:15][CH2:16][C@H:17]([CH3:46])[N:18]3[C:41]([CH:43]2[CH2:45][CH2:44]2)=[O:42])[CH2:11][CH2:10][CH2:9]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 118076364(S)-tert-butyl 4-(4-(5-cyclobutoxy-1-(cyclopropanecarbonyl)-2-methyl-1,2,3,4-tetrahydroquinolin-6-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate

Product 1

HCID 91758779FT-1101 free baseYield 85%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Trifluoroacetic acid (0.5 mL, 6.49 mmol) was added to a 0° C. solution of (S)-tert-butyl 4-(4-(5-cyclobutoxy-1-(cyclopropanecarbonyl)-2-methyl-1,2,3,4-tetrahydroquinolin-6-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate (0.032 g, 0.060 mmol) in dichloromethane (2.0 mL). The ice bath was removed, and the mixture stirred at rt for 1.5 h. The reaction mixture was concentrated, and the residue was partitioned between dichloromethane and saturated aqueous sodium bicarbonate solution. The layers were separated and the organic phase was washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated to afford (S)-(5-cyclobutoxy-2-methyl-6-(1-(piperidin-4-yl)-1H-pyrazol-4-yl)-3,4-dihydroquinolin-1(2H)-yl)(cyclopropyl)methanone (0.022 g, 85%) as an off-white solid. 1H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.57-0.71 (m, 1H), 0.78-0.91 (m, 1H), 0.92-1.04 (m, 1H), 1.13 (d, J=6.45 Hz, 3H), 1.19-1.45 (m, 3H), 1.53-1.71 (m, 2H), 1.79-2.42 (m, 11H), 2.74-2.92 (m, 2H), 2.94-3.09 (m, 1H), 3.30 (br d, J=12.61 Hz, 2H), 4.04-4.21 (m, 1H), 4.28 (ddt, J=11.43, 7.62, 3.96, 3.96 Hz, 1H), 4.66-4.84 (m, 1H), 7.12 (d, J=8.21 Hz, 1H), 7.28 (d, J=8.21 Hz, 1H), 7.81 (s, 1H), 7.88 (s, 1H). MS (ESI, pos. ion) m/z 435 [M+H]+.

Workup

  1. customThe ice bath was removed
  2. concentrationThe reaction mixture was concentrated
  3. customthe residue was partitioned between dichloromethane and saturated aqueous sodium bicarbonate solution
  4. customThe layers were separated
  5. washthe organic phase was washed with brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-a70bbf9ac32744d4a53411f5cf37e624
Source dataset
uspto-grants-2016_07
Patent number
US09388161B2

Reaction notes

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