Ethyl orthoformate → tert-butyl 3-(6-bromo-1H-imidazo[4,5-c]pyridin-1-yl)piperidine-1-carboxylate

HRID 919645Notes

Reaction equation

HRID 919645 reaction equation
[NH2:1][C:2]1[C:3]([NH:9][CH:10]2[CH2:15][CH2:14][CH2:13][N:12]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:11]2)=[CH:4][C:5]([Br:8])=[N:6][CH:7]=1.[CH:23](OCC)(OCC)OCC>>[Br:8][C:5]1[N:6]=[CH:7][C:2]2[N:1]=[CH:23][N:9]([CH:10]3[CH2:15][CH2:14][CH2:13][N:12]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:11]3)[C:3]=2[CH:4]=1

Participants

3

Reactant 2

HCID 31214Ethyl orthoformateHCID 86706485Tert-butyl 3-((5-amino-2-bromopyridin-4-yl)amino)piperidine-1-carboxylate

Product 1

HCID 72344680tert-butyl 3-(6-bromo-1H-imidazo[4,5-c]pyridin-1-yl)piperidine-1-carboxylateYield 70%

Procedure

A mixture of tert-butyl 3-((5-amino-2-bromopyridin-4-yl)amino)piperidine-1-carboxylate (1.1 g, 3.0 mmol, 1.0 eq) in CH(OCH2CH3)3 (214 mg, 30 mmol, 10 eq) was refluxed for 40 h. Then the residual CH(OCH2CH3)3 was removed in vacuum and the crude product was purified by silica gel column chromatography with EtOAc in PE (½ v/v) to give the title compound (0.8 g, 70%) as yellow oil. 1H NMR (400 MHz, CDCl3) δ: 8.87 (s, 1H), 8.06 (s, 1H), 7.62 (s, 1H), 4.30-4.28 (m, 2H), 4.02-4.00 (m, 1H), 3.27-3.22 (m, 1H), 3.09-3.03 (m, 1H), 2.31-2.30 (m, 1H), 2.13-2.10 (m, 1H), 1.88-1.85 (m, 1H), 1.74-1.71 (m, 1H), 1.50 (s, 9H). ESI-MS (M+H+): 381.0.

Workup

  1. temperaturewas refluxed for 40 h
  2. customThen the residual CH(OCH2CH3)3 was removed in vacuum
  3. customthe crude product was purified by silica gel column chromatography with EtOAc in PE (½ v/v)

Sources & evidence

ORD record
ord-1170db8207e944dd85bbd0dd9171b8a2
Source dataset
uspto-grants-2016_03
Patent number
US09273028B2

Reaction notes

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