tert-Butyl 4-((1-(5-cyclopropyl-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-7-yl)ethoxy)methyl)-4-(4-fluorophenyl)piperidine-1-carboxylate → HCID 178467566, compound

HRID 913849Notes

Reaction equation

HRID 913849 reaction equation
[CH:1]1([C:4]2[CH:12]=[C:11]([CH:13]([O:15][CH2:16][C:17]3([C:30]4[CH:35]=[CH:34][C:33]([F:36])=[CH:32][CH:31]=4)[CH2:22][CH2:21][N:20](C(OC(C)(C)C)=O)[CH2:19][CH2:18]3)[CH3:14])[C:10]3[C:6](=[CH:7][N:8](COCC[Si](C)(C)C)[N:9]=3)[CH:5]=2)[CH2:3][CH2:2]1>FC(F)(F)C(O)=O>[CH:1]1([C:4]2[CH:12]=[C:11]([CH:13]([O:15][CH2:16][C:17]3([C:30]4[CH:31]=[CH:32][C:33]([F:36])=[CH:34][CH:35]=4)[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]3)[CH3:14])[C:10]3[C:6](=[CH:7][NH:8][N:9]=3)[CH:5]=2)[CH2:3][CH2:2]1

Participants

3

Reactant 1

HCID 57545980tert-Butyl 4-((1-(5-cyclopropyl-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-7-yl)ethoxy)methyl)-4-(4-fluorophenyl)piperidine-1-carboxylate

Product 1

HCID 178467566HCID 178467566, compoundYield 91%

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Procedure

(±)-tert-Butyl 4-((1-(5-cyclopropyl-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-7-yl)ethoxy)methyl)-4-(4-fluorophenyl)piperidine-1-carboxylate(70.5 mg, 0. 113 mmol) was dissolved in trifluoroacetic acid (50% in dichloromethane, 1 mL) and stirred at room temperature overnight. The reaction was concentrated and loaded onto a strong cation exchange cartridge in methanol. The cartridge was flushed with several volumes of methanol which were discarded. The product was eluted with 2 M ammonia in methanol and concentrated to give 40.5 mg of (±)-5-cyclopropyl-7-(1-((4-(4-fluorophenyl)piperidin-4-yl)methoxy)ethyl)-2H-indazole (91%). The crude amine (40.5 mg, 0. 103 mmol) in dichloromethane (2 mL) was cooled to 0° C. and treated with di-tert-butyl dicarbonate (44.9 mg, 0.206 mmol). The reaction was stirred at 0° C. for 1 h and was quenched by addition of 2 M ammonia in methanol and concentrated. The residue was purified by column chromatography (1%→30% EtOAc/Hex) to give 30 mg (59%) as oil. LC/MS (HPLC method 3): tR=3.15 min, 494.12(MH)+.

Workup

  1. concentrationThe reaction was concentrated
  2. customThe cartridge was flushed with several volumes of methanol which
  3. washThe product was eluted with 2 M ammonia in methanol
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-7abb18130f3346ce8fef8d6990bca3da
Source dataset
uspto-grants-2011_09
Patent number
US08026257B2

Reaction notes

Loading…