Sodium Carbonate → 7-(2-{6-[4-(azetidine-1-sulfonyl)-phenyl]-3H-imidazo[4,5-b]pyridin-2-yl}-ethyl)-azepan-2-one

HRID 1710384Notes

Reaction equation

HRID 1710384 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([S:8]([N:11]2[CH2:14][CH2:13][CH2:12]2)(=[O:10])=[O:9])=[CH:4][CH:3]=1.B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)O1.C([O-])(=O)C.[K+].Br[C:39]1[CH:40]=[C:41]2[N:47]=[C:46]([CH2:48][CH2:49][CH:50]3[NH:56][C:55](=[O:57])[CH2:54][CH2:53][CH2:52][CH2:51]3)[NH:45][C:42]2=[N:43][CH:44]=1.C(=O)([O-])[O-].[Na+].[Na+]>O=O.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].C(Cl)Cl>[N:11]1([S:8]([C:5]2[CH:6]=[CH:7][C:2]([C:39]3[CH:40]=[C:41]4[N:47]=[C:46]([CH2:48][CH2:49][CH:50]5[NH:56][C:55](=[O:57])[CH2:54][CH2:53][CH2:52][CH2:51]5)[NH:45][C:42]4=[N:43][CH:44]=3)=[CH:3][CH:4]=2)(=[O:10])=[O:9])[CH2:14][CH2:13][CH2:12]1

Participants

11

Reactant 5

HCID 10340Sodium CarbonateHCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 72132421-((4-Bromophenyl)sulfonyl)azetidine2×HCID 178516005HCID 178516005, compound2×

Product 1

HCID 1785160077-(2-{6-[4-(azetidine-1-sulfonyl)-phenyl]-3H-imidazo[4,5-b]pyridin-2-yl}-ethyl)-azepan-2-oneYield 46.3%

Reagents, catalysts & solvents 5

HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 977OxygenSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
110 °C

Procedure

378 mg of 1-(4-bromo-benzenesulfonyl)-azetidine (compound C3) are dissolved in 10 ml of oxygen-free dioxane under an atmosphere of dry nitrogen. Subsequently, 383 mg of bis(pinacolato)diboron, 30 mg of Pd(Cl)2(dppf).CH2Cl2, 23 mg of DPPF (1,1′-bis(diphenylphosphino)-ferrocene), and 403 mg of potassium acetate are added. The reaction mixture is heated at 110° C. for 16 hours during which time the former yellowish suspension becomes black (LC-MS monitoring for boronic ester intermediate). Thereafter, 300 mg of 7-[2-(6-bromo-3H-imidazo[4,5-b]pyridin-2-yl)-ethyl]-azepan-2-one (compound C1), 2.70 ml of aqueous sodium carbonate solution (strength 2.0 M), and 66 mg of trans-dichloro-bis(tricyclohexyl-phosphine)-palladium(II) are added and the reaction mixture is heated at 110° C. for 72 hours. Subsequently, the mixture is diluted with 50 ml of water and extracted three times each with 100 ml of dichloromethane. The organic layer is separated, dried using Na2SO4 (solid) and concentrated in vacuo. The resulting crude material is purified by chromatography on flash silica gel (eluent gradient: dichloromethane/0-10 vol. % ethanol) to yield 187 mg of the title compound as an oil. ESI-MS: 454.2 (MH+). TLC: Rf=0.29 (dichloromethane/ethanol 10:1 parts by volume).

Workup

  1. temperaturethe reaction mixture is heated at 110° C. for 72 hours
  2. extractionextracted three times each with 100 ml of dichloromethane
  3. customThe organic layer is separated
  4. customdried
  5. concentrationconcentrated in vacuo
  6. customThe resulting crude material is purified by chromatography on flash silica gel (eluent gradient: dichloromethane/0-10 vol. % ethanol)

Sources & evidence

ORD record
ord-f58e3805f23f4ef8b8d540b3126714e2
Source dataset
uspto-grants-2010_09
Patent number
US07790710B2

Reaction notes

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