(+/-)-tert-Butyl 4-((1-(5-bromo-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-7-yl)ethoxy)methyl)-4-(4-fluorophenyl)piperidine-1-carboxylate → HCID 178467565, compound

HRID 913871Notes

Reaction equation

HRID 913871 reaction equation
[Br:1][C:2]1[CH:10]=[C:9]([CH:11]([O:13][CH2:14][C:15]2([C:28]3[CH:33]=[CH:32][C:31]([F:34])=[CH:30][CH:29]=3)[CH2:20][CH2:19][N:18](C(OC(C)(C)C)=O)[CH2:17][CH2:16]2)[CH3:12])[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>[Br:1][C:2]1[CH:10]=[C:9]([CH:11]([O:13][CH2:14][C:15]2([C:28]3[CH:33]=[CH:32][C:31]([F:34])=[CH:30][CH:29]=3)[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]2)[CH3:12])[C:8]2[C:4](=[CH:5][NH:6][N:7]=2)[CH:3]=1

Participants

3

Reactant 1

HCID 57546111(+/-)-tert-Butyl 4-((1-(5-bromo-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-7-yl)ethoxy)methyl)-4-(4-fluorophenyl)piperidine-1-carboxylate

Product 1

HCID 178467565HCID 178467565, compoundYield 81%

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Procedure

(±)-tert-Butyl 4-((1-(5-bromo-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-7-yl)ethoxy)methyl)-4-(4-fluorophenyl)piperidine-1-carboxylate(380 mg, 0.573 mmol) was dissolved in trifluoroacetic acid (50% in dichloromethane, 6 mL) and stirred at room temperature for 4 h. 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 200 mg of (±)-5-bromo-7-(1-((4-(4-fluorophenyl)piperidin-4-yl)methoxy)ethyl)-2H-indazole (81%). The crude amine (200 mg, 0.463 mmol) in dichloromethane (4 mL) was cooled to 0° C. and treated with di-tert-butyl dicarbonate (202 mg, 0.925 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 200 mg (81%) as clear oil. LC/MS (HPLC method 3): tR=4.046 min, 532.27(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-6087069b755f401a8a015d64b39b0fa9
Source dataset
uspto-grants-2011_09
Patent number
US08026257B2

Reaction notes

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