Tert-butyl6-amino-2-chloro-4-methylnicotinate → tert-Butyl 2-(3-bromophenyl)-5-chloro-7-methylimidazo[1,2-a]pyridine-6-carboxylate

HRID 1481995Notes

Reaction equation

HRID 1481995 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([C:8](OC)(OC)[CH2:9]Br)[CH:3]=1.[NH2:15][C:16]1[CH:28]=[C:27]([CH3:29])[C:19]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])=[C:18]([Cl:30])[N:17]=1>ClC1C=CC=CC=1>[Br:1][C:2]1[CH:3]=[C:4]([C:8]2[N:15]=[C:16]3[CH:28]=[C:27]([CH3:29])[C:19]([C:20]([O:22][C:23]([CH3:25])([CH3:24])[CH3:26])=[O:21])=[C:18]([Cl:30])[N:17]3[CH:9]=2)[CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 117631130Tert-butyl6-amino-2-chloro-4-methylnicotinateHCID 1183088131-Bromo-3-(2-bromo-1,1-dimethoxyethyl)benzene

Product 1

HCID 118308914tert-Butyl 2-(3-bromophenyl)-5-chloro-7-methylimidazo[1,2-a]pyridine-6-carboxylateYield 79.3%

Reagents, catalysts & solvents 1

HCID 7964ChlorobenzeneSolvent

Conditions

Temperature
140 °C

Procedure

A flask charged with chlorobenzene (300 ml) was heated to reflux (140° C. oil bath) and to this was added sequentially 1-bromo-3-(2-bromo-1,1-dimethoxyethyl)benzene (56.05 g, 173 mmol) as an oil, and tert-butyl 6-amino-2-chloro-4-methylnicotinate (33.91 g, 140 mmol) as a powder, rinsing both with additional chlorobenzene (70 mL total) to facilitate transfer. The reaction was returned to reflux and heated for 90 min, then cooled and poured slowly into vigorously stirred Et2O (1500 mL). The resulting suspension was stirred for 15 min, then solids were collected by vacuum filtration to afford the product (47 g, 111 mmol, 64.4% yield) as a tan powdery solid. A 3 g sample of product was first purified by biotage (80 g SiO2, 0% (3 CV), 0-60% (15 CV), 60% (2 CV), EtOAc in hexanes), then recrystallized from hot acetonitrile to afford a high purity sample for spectra. 1H NMR (500 MHz, CDCl3) δ 8.14 (t, J=1.7 Hz, 1H), 8.02 (d, J=0.5 Hz, 1H), 7.89 (dq, J=7.7, 0.9 Hz, 1H), 7.48 (ddd, J=8.0, 2.0, 1.1 Hz, 1H), 7.41-7.39 (m, 1H), 7.32 (t, J=7.9 Hz, 1H), 2.45 (d, J=0.9 Hz, 3H), 1.65 (s, 9H). 13C NMR (126 MHz, CDCl3) δ 164.3, 145.6, 145.2, 135.3, 133.6, 131.3, 130.3, 129.2, 124.7, 123.9, 123.0, 121.7, 115.4, 107.6, 83.9, 28.1, 19.9. LCMS (M+H)=421.3.

Workup

  1. temperaturewas heated
  2. washrinsing both with additional chlorobenzene (70 mL total)
  3. temperatureto reflux
  4. temperatureheated for 90 min
  5. temperaturecooled
  6. additionpoured slowly into vigorously stirred Et2O (1500 mL)
  7. filtrationsolids were collected by vacuum filtration

Sources & evidence

ORD record
ord-2f58fc64e1c24d029e8fc397018b3f8b
Source dataset
uspto-grants-2016_08
Patent number
US09409922B2

Reaction notes

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