(+/-)-tert-Butyl 4-((1-(5-bromo-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-7-yl)ethoxy)methyl)-4-(4-fluorophenyl)piperidine-1-carboxylate → (+/-)-5-Bromo-7-(1-((4-(4-fluorophenyl)piperidin-4-yl)methoxy)ethyl)-1H-indazole

HRID 913847Notes

Reaction equation

HRID 913847 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:3]=[C:4]2[C:8](=[C:9]([CH:11]([O:13][CH2:14][C:15]3([C:28]4[CH:33]=[CH:32][C:31]([F:34])=[CH:30][CH:29]=4)[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]3)[CH3:12])[CH:10]=1)[NH:7][N:6]=[CH:5]2

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 57546134(+/-)-5-Bromo-7-(1-((4-(4-fluorophenyl)piperidin-4-yl)methoxy)ethyl)-1H-indazole

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 (40 mg, 0.075 mmol) was dissolved in trifluoroacetic acid (20% in dichloromethane, 1.25 mL) and stirred at room temperature for 30 min. 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 2M ammonia in methanol and concentrated. 1H-NMR (CDCl3, 500 MHz) δ 10.05 (bs, 1H), 7.90 (s, 1H), 7.73 (d, J=1.5, 1H), 7.25 (m, 2H), 7.10 (d, J=1.5, 1H), 7.05 (m, 2H), 4.48 (q, J=6.4, 1H), 3.39 (d, J=8.9, 1H), 3.25 (d, J=8.9, 1H), 2.91 (m, 1H), 2.84 (m, 1H), 2.75 (m, 1H), 2.68 (m, 1H), 1.60-2.30 (bs, 1H), 2.20 (m, 1H), 2.04 (m, 1H), 1.89 (m, 1H), 1.80 (m, 1H), 1.42 (d, J=6.7, 3H); 13C NMR (126 MHz, CDCl3) δ ppm 162.5, 160.6, 139.5, 135.9, 133.7, 128.7 (d, J=7.7), 128.0, 126.5, 125.5, 122.3, 115.6, 115.4, 113.5, 79.0, 78.2, 50.7, 42.6, 42.5, 41.4, 33.9, 33.6, 22.2.

Workup

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

Sources & evidence

ORD record
ord-86111cab39144799b81bd882ccd0cb96
Source dataset
uspto-grants-2011_09
Patent number
US08026257B2

Reaction notes

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