(+/-)-tert-Butyl 4-((1-(5-dimethylamino-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-7-yl)ethoxy)methyl)-4-(4-fluorophenyl)piperidine-1-carboxylate → HCID 178467569, compound

HRID 913856Notes

Reaction equation

HRID 913856 reaction equation
[CH3:1][N:2]([CH3:44])[C:3]1[CH:11]=[C:10]([CH:12]([O:14][CH2:15][C:16]2([C:29]3[CH:34]=[CH:33][C:32]([F:35])=[CH:31][CH:30]=3)[CH2:21][CH2:20][N:19](C(OC(C)(C)C)=O)[CH2:18][CH2:17]2)[CH3:13])[C:9]2[C:5](=[CH:6][N:7](COCC[Si](C)(C)C)[N:8]=2)[CH:4]=1>FC(F)(F)C(O)=O>[F:35][C:32]1[CH:33]=[CH:34][C:29]([C:16]2([CH2:15][O:14][CH:12]([C:10]3[C:9]4[C:5](=[CH:6][NH:7][N:8]=4)[CH:4]=[C:3]([N:2]([CH3:1])[CH3:44])[CH:11]=3)[CH3:13])[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]2)=[CH:30][CH:31]=1

Participants

3

Reactant 1

HCID 57546051(+/-)-tert-Butyl 4-((1-(5-dimethylamino-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-7-yl)ethoxy)methyl)-4-(4-fluorophenyl)piperidine-1-carboxylate

Product 1

HCID 178467569HCID 178467569, compoundYield 95.1%

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Procedure

(±)-tert-Butyl 4-((1-(5-dimethylamino-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-7-yl)ethoxy)methyl)-4-(4-fluorophenyl)piperidine-1-carboxylate (206 mg, 0.329 mmol) was dissolved in trifluoroacetic acid (50% in dichloromethane, 3.5 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 124 mg of (±)-7-(1-((4-(4-fluorophenyl)piperidin-4-yl)methoxy)ethyl)-N,N-dimethyl-2H-indazol-5-amine (95%). The crude amine (124 mg, 0.313 mmol) in dichloromethane (2.7 mL) was cooled to 0° C. and treated with di-tert-butyl dicarbonate (137 mg, 0.625 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 (18%→45% EtOAc/Hex) to give 138 mg (89%) as clear oil. LC/MS (HPLC method 3): tR=2.816 min, 497.50(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-641746fbe9a1452884a66b82325e8d5b
Source dataset
uspto-grants-2011_09
Patent number
US08026257B2

Reaction notes

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