tert-Butyl 4-(((5-(4-cyanophenyl)-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-7-yl)methoxy)methyl)-4-phenylpiperidine-1-carboxylate → 4-(7-(((4-Phenylpiperidin-4-yl)methoxy)methyl)-1H-indazol-5-yl)benzonitrile

HRID 913981Notes

Reaction equation

HRID 913981 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:17]=[C:16]([CH2:18][O:19][CH2:20][C:21]3([C:34]4[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=4)[CH2:26][CH2:25][N:24](C(OC(C)(C)C)=O)[CH2:23][CH2:22]3)[C:15]3[C:11](=[CH:12][N:13](COCC[Si](C)(C)C)[N:14]=3)[CH:10]=2)=[CH:5][CH:4]=1)#[N:2]>FC(F)(F)C(O)=O>[C:34]1([C:21]2([CH2:20][O:19][CH2:18][C:16]3[CH:17]=[C:9]([C:6]4[CH:5]=[CH:4][C:3]([C:1]#[N:2])=[CH:8][CH:7]=4)[CH:10]=[C:11]4[C:15]=3[NH:14][N:13]=[CH:12]4)[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]2)[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=1

Participants

3

Reactant 1

HCID 57545973tert-Butyl 4-(((5-(4-cyanophenyl)-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-7-yl)methoxy)methyl)-4-phenylpiperidine-1-carboxylate

Product 1

HCID 251596544-(7-(((4-Phenylpiperidin-4-yl)methoxy)methyl)-1H-indazol-5-yl)benzonitrile

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Procedure

tert-Butyl 4-(((5-(4-cyanophenyl)-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-7-yl)methoxy)methyl)-4-phenylpiperidine-1-carboxylate (391 mg, 0.60 mmol) was dissolved in trifluoroacetic acid (50% in dichloromethane, 10 mL) and stirred at room temperature for 2 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 to give 241 mg (95%) as an amorphous solid. 1H-NMR (CDCl3, 500 MHz) δ 8.02 (s, 1H), 7.79 (s, 1H), 7.64 (m, 4H), 7.22-7.50 (m, 7H), 4.73 (s, 2H), 3.57 (s, 2H), 3.41 (s, 1H), 2.90 (m, 2H), 2.75 (m, 2H), 2.19 (m, 2H), 1.88 (m, 2H); 13C-NMR (CDCl3, 126 MHz) δ 145.9, 144.1, 138.6, 134.9, 132.7, 132.0, 129.0, 127.9, 127.1, 126.8, 124.4, 123.7, 121.8, 119.1, 119.0, 110.4, 80.6, 72.0, 42.6, 41.7, 33.6. Mass spec.: 423.18 (MH)+. Accurate mass spec.: m/z 423.2206 [MH]+, Δ=5.0 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. customto give 241 mg (95%) as an amorphous solid

Sources & evidence

ORD record
ord-dd8184cd24304d80b87327c7b2c927ad
Source dataset
uspto-grants-2011_09
Patent number
US08026257B2

Reaction notes

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