HCID 58344958, compound → HCID 58345268, compound

HRID 1887992Notes

Reaction equation

HRID 1887992 reaction equation
[NH2:1][C:2]1[C:7]([C:8]2[N:17]([C:18]3[CH:32]=[CH:31][C:21]([CH2:22][NH:23][C:24](=[O:30])[O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[CH:20][CH:19]=3)[C:11]3=[N:12][CH:13]=[C:14](Br)[CH:15]=[C:10]3[N:9]=2)=[CH:6][CH:5]=[CH:4][N:3]=1>C(O)C.C1(C)C=CC=CC=1>[NH2:1][C:2]1[C:7]([C:8]2[N:17]([C:18]3[CH:32]=[CH:31][C:21]([CH2:22][NH:23][C:24](=[O:30])[O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[CH:20][CH:19]=3)[C:11]3=[N:12][CH:13]=[C:14]([C:7]4[CH:2]=[N:3][CH:4]=[CH:5][CH:6]=4)[CH:15]=[C:10]3[N:9]=2)=[CH:6][CH:5]=[CH:4][N:3]=1

Participants

4

Reactant 1

HCID 58344958HCID 58344958, compound

Product 1

HCID 58345268HCID 58345268, compoundYield 197.5%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

tert-butyl 4-(2-(2-aminopyridin-3-yl)-6-bromo-3H-imidazo[4,5-b]pyridin-3-yl)benzylcarbamate (4 g, 8 mmol) was suspended in a mixture of ethanol and toluene, 160 ml respectively and a solution of NaHCO3sat. was added (27 ml). The reaction mixture was degassed with nitrogen for 30 min. Subsequently it was heated to 100° C. overnight under nitrogen. After cooling down to room temperature it was diluted with 300 ml dichloromethane and 200 ml of water were added. The organic phase was separated and washed with brine (200 ml) and dried over Na2SO4. After filtration the solvent was removed under reduced pressure. The crude residue was purified by silica gel chromatography (2-20% methanol in ethyl acetate). The solvent was removed under reduced pressure, yielding 3.9 g tert-butyl 4-(2-(2-aminopyridin-3-yl)-6-(pyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzylcarbamate (7.9 mmol, 99% yield). 400 M Hz 1H NMR (DMSO-d6) δ: 8.98 (d, J=1.9 Hz, 1H), 8.64 (d, J=2.0 Hz, 1H), 8.59 (dd, J=1.6 Hz and 4.7 Hz, 1H), 8.54 (d, J=2.0 Hz, 1H), 8.20 (m, 1H), 7.98 (m, 1H), 7.52 (m, 2H), 7.48-7.34 (m, 4H), 7.23 (m, 1H), 7.01 (s, br, 2H), 6.38 (m, 1H), 4.19 (m, 2H), 1.38 (s, 9H), MS 438.22, 494.00, [M-(t-Bu)+H, M+H].

Workup

  1. additionwas added (27 ml)
  2. customThe reaction mixture was degassed with nitrogen for 30 min
  3. temperatureAfter cooling down to room temperature it
  4. additionwas diluted with 300 ml dichloromethane and 200 ml of water
  5. additionwere added
  6. customThe organic phase was separated
  7. washwashed with brine (200 ml)
  8. dry with materialdried over Na2SO4
  9. filtrationAfter filtration the solvent
  10. customwas removed under reduced pressure
  11. customThe crude residue was purified by silica gel chromatography (2-20% methanol in ethyl acetate)
  12. customThe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-5bd1926a5a634ad3974d7cce8429e00e
Source dataset
uspto-grants-2013_08
Patent number
US08501770B2

Reaction notes

Loading…