tert-Butyl 4-(((5-bromo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazol-7-yl)methoxy)methyl)-4-phenylpiperidine-1-carboxylate → 5-Bromo-7-(((4-phenylpiperidin-4-yl)methoxy)methyl)-1H-indazole

HRID 913980Notes

Reaction equation

HRID 913980 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([CH2:11][O:12][CH2:13][C:14]3([C:27]4[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=4)[CH2:19][CH2:18][N:17](C(OC(C)(C)C)=O)[CH2:16][CH2:15]3)[CH:10]=1)[N:7](COCC[Si](C)(C)C)[N:6]=[CH:5]2>FC(F)(F)C(O)=O>[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([CH2:11][O:12][CH2:13][C:14]3([C:27]4[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=4)[CH2:15][CH2:16][NH:17][CH2:18][CH2:19]3)[CH:10]=1)[NH:7][N:6]=[CH:5]2

Participants

3

Reactant 1

HCID 57545925tert-Butyl 4-(((5-bromo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazol-7-yl)methoxy)methyl)-4-phenylpiperidine-1-carboxylate

Product 1

HCID 251595255-Bromo-7-(((4-phenylpiperidin-4-yl)methoxy)methyl)-1H-indazole

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Procedure

tert-Butyl 4-(((5-bromo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazol-7-yl)methoxy)methyl)-4-phenylpiperidine-1-carboxylate (40 mg, 0.064 mmol) was dissolved in trifluoroacetic acid (50% in dichloromethane, 3 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 washed with several volumes of methanol which were discarded. The product was eluted with 2 M ammonia in methanol and concentrated. Column chromatography (90:8:4 dichloromethane/methanol/2 M ammonia in methanol) gave 19 mg (75%) as a colorless film. 1H-NMR (CDCl3, 500 MHz) δ 7.87 (s, 1H), 7.74 (d, J=1.8 Hz, 1H), 7.47 (m, 2H), 7.38 (m, 3H), 7.14 (d, J=1.2 Hz, 1H), 4.65 (s, 2H), 3.56 (s, 2H), 2.95 (m, 2H), 2.78 (m, 2H), 2.28 (bs, 1H), 2.22 (m, 2H), 1.88 (m, 2H); 13C-NMR (CDCl3, 126 MHz) δ 143.8, 137.4, 133.6, 129.0, 127.0, 126.8, 125.2, 122.6, 122.5, 113.3, 80.7, 71.7, 42.5, 41.7, 33.5. Mass spec.: 400.01 (MH)+. Accurate mass spec.: m/z 400.1035 [MH]+, Δ=2.6 ppm.

Workup

  1. concentrationThe reaction was concentrated
  2. washThe cartridge was washed with several volumes of methanol which
  3. washThe product was eluted with 2 M ammonia in methanol
  4. concentrationconcentrated
  5. customColumn chromatography (90:8:4 dichloromethane/methanol/2 M ammonia in methanol) gave 19 mg (75%) as a colorless film

Sources & evidence

ORD record
ord-0ec64e895a204f2488f307d5b49528ed
Source dataset
uspto-grants-2011_09
Patent number
US08026257B2

Reaction notes

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