HCID 178451735, compound → Tert-butyl 5-(1-(tert-butoxycarbonyl)piperidin-4-yl)-3-iodo-1h-indazole-1-carboxylate

HRID 1520018Notes

Reaction equation

HRID 1520018 reaction equation
[I:1][C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([CH:11]3[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13][CH2:12]3)[CH:9]=2)[NH:4][N:3]=1>C(#N)C>[C:20]([O:19][C:17]([N:14]1[CH2:15][CH2:16][CH:11]([C:8]2[CH:9]=[C:10]3[C:5](=[CH:6][CH:7]=2)[N:4]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[N:3]=[C:2]3[I:1])[CH2:12][CH2:13]1)=[O:18])([CH3:23])([CH3:22])[CH3:21]

Participants

3

Reactant 1

HCID 178451735HCID 178451735, compound

Product 1

HCID 67981049Tert-butyl 5-(1-(tert-butoxycarbonyl)piperidin-4-yl)-3-iodo-1h-indazole-1-carboxylateYield 148.7%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A solution of tert-butyl 4-(3-iodo-1H-indazol-5-yl)piperidine-1-carboxylate (218. mg; 0.51 mmol; 1.0 eq.), di-tert-butyldicarboxylate (145 mg; 0.66 mmol; 1.3 eq.), diméthylamino-4-pyridine (12.5 mg; 0.10 mmol; 0.20 eq.) and TEA (86.0 μl; 0.61 mmol; 1.2 eq.) in acetonitrile (6.5 mL) was stirred at RT O/N. Acetonitrile was removed under reduced pressure, the residue was diluted with water and extracted three times with Ether. Combined organic phases were washed with brine, dried over magnesium sulfate, filtered and concentrated. The crude was purified by flash chromatography on silica (heptane/EtOAc, gradient from 90:10 to 75:25) to give the title compound as a colorless oil (200 mg, 74%). 1H NMR (300 MHz, DMSO-d6) δ 7.99 (d, J=8.7 Hz, 1H), 7.62 (dd, J=1.6, 8.7 Hz, 1H), 7.35 (s, 1H), 4.18-4.03 (m, 2H), 2.96-2.73 (m, 3H), 1.87-1.75 (m, 2H), 1.64 (s, 9H). 1.61-1.48 (m, 2H), 1.42 (s, 9H). (Condition A): Rt 6.33 min (purity 99.8%).

Workup

  1. customAcetonitrile was removed under reduced pressure
  2. additionthe residue was diluted with water
  3. extractionextracted three times with Ether
  4. washCombined organic phases were washed with brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude was purified by flash chromatography on silica (heptane/EtOAc, gradient from 90:10 to 75:25)

Sources & evidence

ORD record
ord-16a6b0ba1a0442c394c26ce5030eabf1
Source dataset
uspto-grants-2015_07
Patent number
US09073892B2

Reaction notes

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