HCID 57546118, compound → HCID 57546152, compound

HRID 913920Notes

Reaction equation

HRID 913920 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]([CH:11]([O:16][CH2:17][C:18]2([C:31]3[CH:36]=[CH:35][C:34]([F:37])=[CH:33][CH:32]=3)[CH2:23][CH2:22][N:21]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:20][CH2:19]2)[C:12]([O:14][CH3:15])=[O:13])[C:8]2[C:4](=[CH:5][N:6](COCC[Si](C)(C)C)[N:7]=2)[CH:3]=1>FC(F)(F)C(O)=O>[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([CH:11]([O:16][CH2:17][C:18]3([C:31]4[CH:32]=[CH:33][C:34]([F:37])=[CH:35][CH:36]=4)[CH2:23][CH2:22][N:21]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:20][CH2:19]3)[C:12]([O:14][CH3:15])=[O:13])[CH:10]=1)[NH:7][N:6]=[CH:5]2

Participants

3

Reactant 1

HCID 57546118HCID 57546118, compound

Product 1

HCID 57546152HCID 57546152, compound

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Procedure

tert-Butyl 4-((1-(5-chloro-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-7-yl)-2-methoxy-2-oxoethoxy)methyl)-4-(4-fluorophenyl)piperidine-1-carboxylate (25 mg) was stirred in trifluoroacetic acid (50% in dichloromethane, 1.5 mL) for 4 h and concentrated. The residue was loaded onto a strong cation exchange cartridge and washed with several volumes of methanol. The product was eluted with 2M ammonia in methanol and concentrated. The crude piperidine was dissolved in dichloromethane (1 mL) and treated with di-tert-butyldicarbonate (17 mg). After 15 min, the reaction was quenched by addition of 2 M ammonia in methanol and concentrated. Column chromatography (ethyl acetate/n-hexane) gave the title compound. 1H-NMR (CDCl3, 500 MHz) δ 10.14 (bs, 1H), 7.93 (s, 1H), 7.66 (d, J=1.8, 1H), 7.29 (dd, J=8.2, 5.2, 2H), 7.07 (dd, J=8.9, 8.5, 2H), 4.85 (s, 1H), 3.50-3.80 (m, 6H), 3.36 (d, J=8.5, 1H), 3.02 (m, 2H), 2.15 (m, 2H), 1.81 (m, 2H), 1.42 (s, 9H); 13C NMR (126 MHz, CDCl3) δ ppm 169.8, 161.7 (d, J=247 Hz), 155.0, 137.82, 137.79, 136.0, 133.7, 128.8 (d, J=7.7 Hz), 126.2, 126.1, 125.0, 120.8, 119.5, 115.7 (d,J=21 Hz), 80.7, 79.6, 79.0, 52.7, 41.3, 39.9 (br), 32.3, 32.2, 28.5.

Workup

  1. concentrationconcentrated
  2. washwashed with several volumes of methanol
  3. washThe product was eluted with 2M ammonia in methanol
  4. concentrationconcentrated
  5. dissolutionThe crude piperidine was dissolved in dichloromethane (1 mL)
  6. additiontreated with di-tert-butyldicarbonate (17 mg)
  7. customthe reaction was quenched by addition of 2 M ammonia in methanol
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-ea8bd8bdffd149d885188a4147be1694
Source dataset
uspto-grants-2011_09
Patent number
US08026257B2

Reaction notes

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