3-(1,3,2-Dioxaborinan-2-yl)pyridine → tert-butyl 4-{[4-amino-2-ethyl-7-(pyridin-3-yl)-1H-imidazo[4,5-c]quinolin-1-yl]methyl}piperidine-1-carboxylate

HRID 1818192Notes

Reaction equation

HRID 1818192 reaction equation
[NH2:1][C:2]1[C:11]2[N:12]=[C:13]([CH2:29][CH3:30])[N:14]([CH2:15][CH:16]3[CH2:21][CH2:20][N:19]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:18][CH2:17]3)[C:10]=2[C:9]2[CH:8]=[CH:7][C:6](Br)=[CH:5][C:4]=2[N:3]=1.B1([C:38]2[CH:43]=[CH:42][CH:41]=[N:40][CH:39]=2)OCCCO1>O>[NH2:1][C:2]1[C:11]2[N:12]=[C:13]([CH2:29][CH3:30])[N:14]([CH2:15][CH:16]3[CH2:21][CH2:20][N:19]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:18][CH2:17]3)[C:10]=2[C:9]2[CH:8]=[CH:7][C:6]([C:38]3[CH:39]=[N:40][CH:41]=[CH:42][CH:43]=3)=[CH:5][C:4]=2[N:3]=1

Participants

4

Reactant 2

HCID 41980053-(1,3,2-Dioxaborinan-2-yl)pyridineHCID 21984269tert-Butyl 4-[(4-amino-7-bromo-2-ethyl-1H-imidazo[4,5-c]quinolin-1-yl)methyl]piperidine-1-carboxylate

Product 1

HCID 21984221tert-butyl 4-{[4-amino-2-ethyl-7-(pyridin-3-yl)-1H-imidazo[4,5-c]quinolin-1-yl]methyl}piperidine-1-carboxylateYield 59.2%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

tert-Butyl 4-[(4-amino-7-bromo-2-ethyl-1H-imidazo[4,5-c]quinolin-1-yl)methyl]piperidine-1-carboxylate (9.24 g, 18.9 mmol) and pyridine-3-boronic acid 1,3-propanediol cyclic ester (3.39 g, 20.8 mmol) were coupled according to the method described in Examples 118-121. Additional reagents were added after the reaction was heated for 16 hours, and the reaction was continued for 16 hours. Water (20 mL) was added, and the n-propanol was removed under reduced pressure. The remaining mixture was extracted with chloroform (2×200 mL), and the combined organic fractions were purified by column chromatography on silica gel (eluting with chloroform and chloroform:CMA). The resulting solid was recrystallized from acetonitrile to provide 5.44 g of tert-butyl 4-{[4-amino-2-ethyl-7-(pyridin-3-yl)-1H-imidazo[4,5-c]quinolin-1-yl]methyl}piperidine-1-carboxylate as a white, fluffy solid, mp 229-231° C.

Workup

  1. additionAdditional reagents were added after the reaction
  2. temperaturewas heated for 16 hours
  3. customthe n-propanol was removed under reduced pressure
  4. extractionThe remaining mixture was extracted with chloroform (2×200 mL)
  5. customthe combined organic fractions were purified by column chromatography on silica gel (eluting with chloroform and chloroform:CMA)
  6. customThe resulting solid was recrystallized from acetonitrile

Sources & evidence

ORD record
ord-7be389a1b46347808131044b3da7e6a7
Source dataset
uspto-grants-2009_10
Patent number
US07598382B2

Reaction notes

Loading…