Trimethylsilyl iodide → 4-[2-(4-Fluorophenyl)-7-piperidin-4-ylimidazo-[1,2-a]pyridin-3-yl]piperidin-2-ylamine

HRID 1785400Notes

Reaction equation

HRID 1785400 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([C:8]2[N:12]3[CH:13]=[CH:14][C:15]([CH:17]4[CH2:22][CH2:21][N:20](C(OCC5C=CC=CC=5)=O)[CH2:19][CH2:18]4)=[CH:16][C:11]3=[N:10][C:9]=2[C:33]2[CH:38]=[CH:37][C:36]([F:39])=[CH:35][CH:34]=2)[CH:5]=[CH:4][N:3]=1.[Si](I)(C)(C)C>CC#N>[F:39][C:36]1[CH:35]=[CH:34][C:33]([C:9]2[N:10]=[C:11]3[CH:16]=[C:15]([CH:17]4[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]4)[CH:14]=[CH:13][N:12]3[C:8]=2[C:6]2[CH:5]=[CH:4][N:3]=[C:2]([NH2:1])[N:7]=2)=[CH:38][CH:37]=1

Participants

4

Reactant 2

HCID 85247Trimethylsilyl iodideHCID 69055315HCID 69055315, compound

Product 1

HCID 248874184-[2-(4-Fluorophenyl)-7-piperidin-4-ylimidazo-[1,2-a]pyridin-3-yl]piperidin-2-ylamine

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

Benzyl carbonate 37 (190 mg, 0.36 mmol) was slurried in CH3CN (5 mL) in a 28 mL Pyrex Plus tube. TMSI (720 mg, 3.6 mmol) was then added, and the reaction was allowed to stir at room temperature for 2 hours. The reaction was then concentrated under reduced pressure. The crude product was then dissolved in 10 mL CH2Cl2, plus a few drops of methanol, then loaded onto a 40 g Isco RediSep normal phase silica cartridge, and purified on an Isco OptiX10 CombiFlash instrument using a gradient that started at 100% methylene chloride and ended at 90% methylene chloride, 9% methanol, 1% concentrated ammonium hydroxide. Fractions containing desired product were pooled and concentrated under reduced pressure. Yield of 38: 140 mg (100%). 1H NMR (400 MHz, CDCl3) δ 1.67 (m, 2H), 1.84 (m, 2H), 2.67 (m, 1H), 2.74 (m, 2H), 3.18 (m, 2H), 5.03 (s, 2H), 6.44 (d, J=5.2 Hz, 1H), 6.77 (d, J=7.2 Hz, 1H), 7.05 (t, J=8.8 Hz, 2H), 7.43 (bs, 1H), 7.56 (m, 2H), 8.04 (d, J=5.2 Hz, 1H), 9.36 (d, J=7.2 Hz, 1H). MS (ESI+) 389.2.

Workup

  1. concentrationThe reaction was then concentrated under reduced pressure
  2. dissolutionThe crude product was then dissolved in 10 mL CH2Cl2
  3. custompurified on an Isco OptiX10 CombiFlash instrument
  4. additionFractions containing desired product
  5. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-3aced184e76142c7b010866d410568c4
Source dataset
uspto-grants-2009_03
Patent number
US07504501B2

Reaction notes

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